The Distribution and Movement of American Cockroaches in Urban Niches of New Orleans.

Science.gov (United States)

Carlson, John C; Rabito, Felicia A; Werthmann, Derek; Fox, Mark

2017-10-01

American cockroaches are an important source of household allergens in tropical and semitropical climates. To determine which outdoor niches produce American cockroaches, traps were placed at 40 homes in New Orleans to collect nymphs. Nymphs were collected from the sewers, yards, and within the homes themselves. To compare sewers and yards as sources of cockroaches entering homes, adult cockroaches were collected, marked, and released into yards and sewers. No sewer-released cockroaches were collected in homes. Cockroaches released into yards were collected in the homes, suggesting that yards, rather than sewers, are a more important source niche. A field trial applying boric acid granules to the yard was performed in an effort to reduce entry of cockroaches. There was a significant reduction in the cockroach antigen collected in intervention homes compared with controls.

Life history and habitat associations of the broad wood cockroach, Parcoblatta lata (Blattaria: Blattellidae) and other native cockroaches in the Coastal Plain of South Carolina.

Energy Technology Data Exchange (ETDEWEB)

Horn, Scott; Hanula, James, L.

2002-06-18

Wood cockroaches are an important prey of the red-cockaded woodpecker, Picoides borealis, an endangered species inhabiting pine forests in the southern United States. These woodpeckers forage on the boles of live pine trees, but their prey consists of a high proportion of wood cockroaches, Parcoblatta spp., that are more commonly associated with dead plant material. Cockroach population density samples were conducted on live pine trees, dead snags and coarse woody debris on the ground. The studies showed that snags and logs are also important habitats of wood cockroaches in pine forests.

Contamination of cockroaches (Insecta: Blattaria) to medically fungi: A systematic review and meta-analysis.

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Nasirian, H

2017-12-01

Fungal infections have emerged worldwide. Cockroaches have been proved vectors of medically fungi. A systematic meta-analysis review about cockroach fungal contamination was investigated. Relevant topics were collected between January 2016 and January 2017. After a preliminary review among 392 collected papers, 156 were selected to become part of the detailed systematic meta-analysis review. Cockroaches contaminated to 38 fungi species belonging to 19 families and 12 orders. About 38, 25 and 13 fungal species were recovered from the American, German and brown-banded cockroaches, respectively with a variety of medical importance. Except the fungi isolated from German and brown-banded cockroaches, 15 species have been isolated only from the American cockroaches. The global world mean and trend of cockroach fungal contamination were 84.1 and 50.6-100%, respectively in the human dwelling environments. There is a significant difference between cockroach fungal contamination in the urban and rural environments (P0.05). The external and internal cockroach fungal contamination is more dangerous than entire surfaces, while the internal is more dangerous than the external surface. The German and brown-banded cockroach fungal contamination are more dangerous than the American cockroaches in the hospital environments. The study indicates that globally cockroach fungal contamination has been increased recognizing as agents of human infections and associating with high morbidity and mortality in immune-compromised patients. These facts, along with insecticide resistance emergence and increasing globally cockroach infestation, reveal importance of cockroaches and need for their control more than ever. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Medically Important Parasites Carried by Cockroaches in Melong Subdivision, Littoral, Cameroon

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R. J. Atiokeng Tatang

2017-01-01

Full Text Available Cockroaches have been recognized as mechanical vectors of pathogens that can infest humans or animals. A total of 844 adult cockroaches (436 males and 408 females were caught. In the laboratory, cockroaches were first washed in saturated salt solution to remove ectoparasites and then rinsed with 70% alcohol, dried, and dissected for endoparasites. An overall transport rate of 47.39% was recorded. Six genera of parasites were identified. These were Ascaris (33.76%, Trichuris (11.97%, Capillaria (6.16%, Toxocara (4.86%, Hook Worm (4.86%, and Eimeria (2.73%. The parasites were more recorded on the external surface (54.27% of cockroaches than in the internal surface (GIT, 38.51%. The same tendency was obtained between sexes with female cockroaches having a higher transport rate (36.69%. Cockroaches caught in toilets carried more parasites (31.99% as compared to those from kitchens (22.63% and houses (11.14%. Almost all encountered parasites were recognized as responsible of zoonosis and they can be consequently released in nature by hosts and easily disseminated by cockroaches as mechanical vectors. Sanitary education, reenforcement of worms’ eradication programs, and the fight against these insects remain a necessity in the Mélong Subdivision.

Investigation on American cockroaches medically important bacteria in Khorramshahr hospital, Iran

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Hamid Kassiri

2014-06-01

Full Text Available Objective: To investigate American cockroaches' infection to various bacteria in Khorramshahr Vali-e-Asr hospital, which was done in 2008. Methods: In this descriptive cross-sectional study, 20 American cockroaches were caught via direct collection. Medically important bacteria were extracted from their outer surface of bodies by standard procedures. Results: Culturing outer surface wash of cockroaches resulted in the separation of Klebsiella, Pseudomonas, Escherichia coli, Staphylococcus, Proteus and Streptococcus. The main common bacteria were Klebsiella (35% and Pseudomonas (30%. Also, results of culture media showed that about 90% of cockroaches infected to at least one bacterium. Conclusions: American cockroaches can transmit pathogenic and potential pathogenic bacteria, therefore their presence in hospitals may be a sanitation challenge. It is recommended to assess plans in purpose to combat these pests in the hospitals.

Food-borne human parasitic pathogens associated with household cockroaches and houseflies in Nigeria

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Oyetunde T. Oyeyemi

2016-03-01

Full Text Available Cockroaches and houseflies pose significant public health threat owning to their ability to mechanically transmit human intestinal parasites and other disease-causing microorganisms. This study aims at assessing the vectoral capacity of cockroaches and houseflies in the transmission of human intestinal parasites. Intestinal parasite external surface contamination of 130 cockroaches and 150 houseflies caught within dwelling places in Ilishan-Remo town, Ogun State, Nigeria was determined. Cockroaches (six parasite species were more contaminated than houseflies (four parasite species. The most prevalent parasites were Trichuris trichiura (74.0% and hookworm (63.0% in houseflies and cockroaches respectively. There were significant differences in the prevalence of hookworm, T. trichiura and Taenia spp. isolated from cockroaches and houseflies (P < 0.05. There is high contamination of human intestinal parasites in cockroaches and houseflies in human dwelling places in the study area, thus they have the ability to transmit these parasites to unkempt food materials.

Static electric fields modify the locomotory behaviour of cockroaches.

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Jackson, Christopher W; Hunt, Edmund; Sharkh, Suleiman; Newland, Philip L

2011-06-15

Static electric fields are found throughout the environment and there is growing interest in how electric fields influence insect behaviour. Here we have analysed the locomotory behaviour of cockroaches (Periplaneta americana) in response to static electric fields at levels equal to and above those found in the natural environment. Walking behaviour (including velocity, distance moved, turn angle and time spent walking) were analysed as cockroaches approached an electric field boundary in an open arena, and also when continuously exposed to an electric field. On approaching an electric field boundary, the greater the electric field strength the more likely a cockroach would be to turn away from, or be repulsed by, the electric field. Cockroaches completely exposed to electric fields showed significant changes in locomotion by covering less distance, walking slowly and turning more often. This study highlights the importance of electric fields on the normal locomotory behaviour of insects.

Cockroaches (Blattaria) of Ecuador-checklist and history of research.

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Vidlička, Lubomír

2013-01-09

Cockroaches are an understudied group and the total number of described taxa increases every year. The last checklist of Ecuador species was published in 1926. The main aim of this study was to complete a new checklist of cockroach species recorded in Ecuador supplemented with a research history of cockroaches (Blattaria) on the territory of continental Ecuador. In addition, the checklist contains comments on Ecuadorian faunistic records, including the Galápagos Islands. A total of 114 species (105 in continental Ecuador and 18 in Galápagos Islands) belonging to 6 families and 44 genera are listed. Forty species (38.1 %) occur solely in continental Ecuador and five (27.8 %) are endemic on Galápagos Islands. The results indicate that further research on the cockroach fauna of Ecuador as well as determination of museum collections from this territory is needed.

Quality of housing and allergy to cockroaches in the Dominican Republic.

Science.gov (United States)

Barnes, K C; Brenner, R J

1996-01-01

Fifty-one atopic asthmatic and/or allergic rhinitic children and 23 nonatopic control from Santo Domingo, the Dominican Republic, were skin tested with an extract mix of three cockroach species (Blattella germanica, Blatta orientalis, and Periplaneta americana). Sixteen percent of the atopics and none of the nonatopics demonstrated positive immediate skin reactions to the cockroach mix (chi 2 = 4.05, p = 0.04). Hypersensitivity was correlated with the quality of the homes; 22% (8/36) of the atopics who lived in a concrete home were skin test positive to the cockroach mix, while none (0/15) of the atopics who lived in a wood home were skin test positive (chi 2 = 4.86, p = 0.03). Although the incidence of cockroach allergy in this study is lower than that found elsewhere, these data support the notion that, in this tropical environment, sensitization to cockroaches is associated with housing quality.

Binary Cockroach Swarm Optimization for Combinatorial Optimization Problem

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Ibidun Christiana Obagbuwa

2016-09-01

Full Text Available The Cockroach Swarm Optimization (CSO algorithm is inspired by cockroach social behavior. It is a simple and efficient meta-heuristic algorithm and has been applied to solve global optimization problems successfully. The original CSO algorithm and its variants operate mainly in continuous search space and cannot solve binary-coded optimization problems directly. Many optimization problems have their decision variables in binary. Binary Cockroach Swarm Optimization (BCSO is proposed in this paper to tackle such problems and was evaluated on the popular Traveling Salesman Problem (TSP, which is considered to be an NP-hard Combinatorial Optimization Problem (COP. A transfer function was employed to map a continuous search space CSO to binary search space. The performance of the proposed algorithm was tested firstly on benchmark functions through simulation studies and compared with the performance of existing binary particle swarm optimization and continuous space versions of CSO. The proposed BCSO was adapted to TSP and applied to a set of benchmark instances of symmetric TSP from the TSP library. The results of the proposed Binary Cockroach Swarm Optimization (BCSO algorithm on TSP were compared to other meta-heuristic algorithms.

Rapid Elimination of German Cockroach, Blatella germanica, by Fipronil and Imidacloprid Gel Baits

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H Nasirian

2008-08-01

Full Text Available Background: Baits have become popular and effective formulations against urban insect pests. Compared with re­sidual sprays toxic gel baits are used more and more frequently to control urban cockroach populations. The aim of this study was to investigate the usage of two commercially available fipronil and imidacloprid gel bait formulations against Blattella germanica field infested in Iran. Methods:  The study was carried out in an urban area at Tehran from March 2004 to September 2005. The 0.05% fipronil and 2.15% imidacloprid gel baits were placed continuously in 3 residential German cockroach infested units. Pre- and post-treatment cockroach density was assessed by visual count method. Results: Pre- and post-treatment visual count of cockroaches in treatment and control areas, and percentage reduc­tion in cockroach density in treatment areas in comparison to control areas was showed that density reduction was increased with the 0.05% fipronil and 2.15% imidacloprid gel baits in treated areas from 1st to 9th week in compari­son to control area. After 60 days, German cockroaches eliminated completely from these areas. Conclusion: These results show that fipronil and imidacloprid gel baits are highly effective in field German cock­roach infested after insecticide spraying control failure German cockroach infested fields where spraying  of pyrethroid insecticides failed to control the situation and confirm previous  reports stating that avermectin and hydramethylnon are more effective than conventional insecticides in baits against cockroaches. Therefore, fipronil and imidacloprid gel baits are appropriate candidates for controlling German cockroach infested dwellings in Iran where control with other insectices failed because of resistance.

Rapid Elimination of German Cockroach, Blatella germanica, by Fipronil and Imidacloprid Gel Baits

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H Nasirian

2008-06-01

Full Text Available Background: Baits have become popular and effective formulations against urban insect pests. Compared with re­sidual sprays toxic gel baits are used more and more frequently to control urban cockroach populations. The aim of this study was to investigate the usage of two commercially available fipronil and imidacloprid gel bait formulations against Blattella germanica field infested in Iran.Methods:  The study was carried out in an urban area at Tehran from March 2004 to September 2005. The 0.05% fipronil and 2.15% imidacloprid gel baits were placed continuously in 3 residential German cockroach infested units. Pre- and post-treatment cockroach density was assessed by visual count method.Results: Pre- and post-treatment visual count of cockroaches in treatment and control areas, and percentage reduc­tion in cockroach density in treatment areas in comparison to control areas was showed that density reduction was increased with the 0.05% fipronil and 2.15% imidacloprid gel baits in treated areas from 1st to 9th week in compari­son to control area. After 60 days, German cockroaches eliminated completely from these areas.Conclusion: These results show that fipronil and imidacloprid gel baits are highly effective in field German cock­roach infested after insecticide spraying control failure German cockroach infested fields where spraying  of pyrethroid insecticides failed to control the situation and confirm previous  reports stating that avermectin and hydramethylnon are more effective than conventional insecticides in baits against cockroaches. Therefore, fipronil and imidacloprid gel baits are appropriate candidates for controlling German cockroach infested dwellings in Iran where control with other insectices failed because of resistance.

Cockroaches ’ bacterial infections in wards of hospitals, Hamedan city, west of Iran

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Nejati Jalil

2012-10-01

Full Text Available Objective: To identify the relationship between different species of cockroaches with their bacterial infection in different wards of Hamedan county hospitals, western Iran. Methods: Using sticky trap, hand collection and glass trap, 250 cockroaches were collected from 14 wards of 5 hospitals. After having their identification determined by detection key, all of them were used to isolate bacteria from cuticle and alimentary tract. Results: From four identified species, Blatella germanica were the most common in all of the wards (88.8% and next was the Periplaneta Americana (8%. 20 bacteria species isolated from cockroaches' surface and 21 from digestive organ. Escherichia coli were the most predominant bacteria isolated from external surface (26.5 % as well as alimentary tract (30.8%. The frequency of investigated bacteria on cockroaches' body surface was not significantly different between Periplaneta Americana and Blattella germanica except for Kllebsiella oxytoca (P<0.001 and Providensia Spp (P=0.035. Also, frequency of detected bacteria in cockroaches' digestive organ was not significantly different between these two species. Furthermore, the frequency of bacteria isolated from the cockroaches' external surface was not significantly different from that of digestive organ except for shigella disantery (P<0.001, Pseudomonas aeroginosa (P<0.001 and Klebsiella oxytoca (P=0.01 3. Conclusions: Since cockroaches can carry pathogenic bacteria, so their existence in the hospitals could be a serious public health problem. It is suggested to compile programs in order to control cockroaches especially in the hospitals.

There are more asthmatics in homes with high cockroach infestation

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Sarinho E.

2004-01-01

Full Text Available Although asthma has been commonly associated with sensitivity to cockroaches, a clear causal relationship between asthma, allergy to cockroaches and exposure levels has not been extensively investigated. The objective of the present study was to determine whether asthma occurs more frequently in children living in homes with high cockroach infestation. The intensity of household infestation was assessed by the number of dead insects after professional pesticide application. Children living in these houses in the metropolitan area of Recife, PE, were diagnosed as having asthma by means of a questionnaire based on the ISAAC study. All children had physician-diagnosed asthma and at least one acute exacerbation in the past year. Children of both sexes aged 4 to 12 years who had been living in the households for more than 2 years participated in this transverse study and had a good socioeconomic status. In the 172 houses studied, 79 children were considered to have been exposed to cockroaches and 93 not to have been exposed. Children living in residences with more than 5 dead cockroaches after pesticide application were considered to be at high infestation exposure. Asthma was diagnosed by the questionnaire in 31.6% (25/79 of the exposed group and in 11.8% (11/93 of the non-exposed group (P = 0.001, with a prevalence ratio of 3.45 (95%CI, 1.48-8.20. The present results indicate that exposure to cockroaches was significantly associated with asthma among the children studied and can be considered a risk factor for the disease. Blattella germanica and Periplaneta americana were the species found in 96% of the infested houses.

Modelling active antennal movements of the American cockroach

DEFF Research Database (Denmark)

Pequeno-Zurro, Alejandro; Nitschke, Jahn; Szyszka, Paul

2017-01-01

lacking. Here we report on an integrated experimental and computational approach to investigate how sensory information affects antennal movements. We present a modelling approach to characterise the relationship between antennal searching movement of the American cockroach Periplaneta americana......Cockroach antennae are multimodal sensory appendages engaging in active olfactory and tactile sensing. They are involved in unisensory behaviours such as chemotaxis, thigmotaxis, obstacle negotiation and tactile orientation. Studies of multisensory capabilities mediated by the antennae are however...

Agonist actions of clothianidin on synaptic and extrasynaptic nicotinic acetylcholine receptors expressed on cockroach sixth abdominal ganglion.

Science.gov (United States)

Thany, Steeve H

2009-11-01

Clothianidin is new neonicotinoid insecticide acting selectively on insect nicotinic acetylcholine receptors (nAChRs). Its effects on nAChRs expressed on cercal afferent/giant interneuron synapses and DUM neurons have been studied using mannitol-gap and whole-cell patch-clamp techniques, respectively. Bath-application of clothianidin-induced dose-dependent depolarizations of cockroach cercal afferent/giant interneuron synapses which were not reversed after wash-out suggesting a strong desensitization of postsynaptic interneurons at the 6th abdominal ganglion (A6). Clothinidin activity on the nerve preparation was characterized by an increased firing rate of action potentials which then ceased when the depolarization reached a peak. Clothianidin responses were insensitive to all muscarinic antagonists tested but were blocked by co-application of specific nicotinic antagonists methyllicaconitine, alpha-bungarotoxin and d-tubocurarine. In a second round of experiment, clothianidin actions were tested on DUM neurons isolated from the A6. There was a strong desensitization of nAChRs which was not affected by muscarinic antagonists, pirenzepine and atropine, but was reduced with nicotinic antagonist alpha-bungarotoxin. In addition, clothianidin-induced currents were completely blocked by methyllicaconitine suggesting that (1) clothianidin acted as a specific agonist of nAChR subtypes and (2) a small proportion of receptors blocked by MLA was insensitive to alpha-bungarotoxin. Moreover, because clothianidin currents were blocked by d-tubocurarine and mecamylamine, we provided that clothianidin was an agonist of both nAChRs: imidacloprid-sensitive nAChR1 and -insensitive nAChR2 subtypes.

Genetic diversity of Entamoeba: Novel ribosomal lineages from cockroaches.

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Tetsuro Kawano

Full Text Available Our current taxonomic perspective on Entamoeba is largely based on small-subunit ribosomal RNA genes (SSU rDNA from Entamoeba species identified in vertebrate hosts with minor exceptions such as E. moshkovskii from sewage water and E. marina from marine sediment. Other Entamoeba species have also been morphologically identified and described from non-vertebrate species such as insects; however, their genetic diversity remains unknown. In order to further disclose the diversity of the genus, we investigated Entamoeba spp. in the intestines of three cockroach species: Periplaneta americana, Blaptica dubia, and Gromphadorhina oblongonota. We obtained 134 Entamoeba SSU rDNA sequences from 186 cockroaches by direct nested PCR using the DNA extracts of intestines from cockroaches, followed by scrutinized BLASTn screening and phylogenetic analyses. All the sequences identified in this study were distinct from those reported from known Entamoeba species, and considered as novel Entamoeba ribosomal lineages. Furthermore, they were positioned at the base of the clade of known Entamoeba species and displayed remarkable degree of genetic diversity comprising nine major groups in the three cockroach species. This is the first report of the diversity of SSU rDNA sequences from Entamoeba in non-vertebrate host species, and should help to understand the genetic diversity of the genus Entamoeba.

Chow Down! Using Madagascar Hissing Cockroaches to Explore Basic Nutrition Concepts

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Wagler, Ron

2009-01-01

The Madagascar hissing cockroach ("Gromphadorhina portentosa") is one of the most exciting and enjoyable animals to incorporate into your science curriculum. Madagascar hissing cockroaches (MHCs) do not bite, are easy to handle, produce little odor compared to many terrarium animals, have a fascinating social structure, are easy to breed, teach…

Isolation of Intestinal Parasites of Public Health Importance from Cockroaches (Blattella germanica) in Jimma Town, Southwestern Ethiopia

OpenAIRE

Hamu, Haji; Debalke, Serkadis; Zemene, Endalew; Birlie, Belay; Mekonnen, Zeleke; Yewhalaw, Delenasaw

2014-01-01

Cockroaches are claimed to be mechanical transmitters of disease causing microorganisms such as intestinal parasites, bacteria, fungi, and viruses. This study assessed the potential of the German cockroach Blattella germanica in the mechanical transmission of intestinal parasites of public health importance. A total of 2010 cockroaches were collected from 404 households in Jimma Town, southwestern Ethiopia. All the collected cockroaches were identified to species as B. germanica. The contents...

Biocontrol of the Brown-banded Cockroach, Supella longipalpa F. (Blattaria: Blattellidae, with Entomopathogenic Fungus, Metharhizium anisopliae

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Mona Sharififard

2016-01-01

Full Text Available Background: Considering to the high distribution of cockroaches as urban pests, the efficacy of different formula­tions of Metarhizium anisopliae strain Iran 437C were assessed against the brown-banded cockroach, Supella longi­palpa F. under laboratory and field conditions.Methods: Metarhizium anisopliae isolates were screened with immersing adults of the brown-banded cockroachs in aqueous suspension of 108 conidia ml-1 followed by surface or bait treated with different doses of the most virulent isolate against the nymphs. Then formulations of conidia oil-in-water were examined versus cockroach nymphs us­ing different plant oils and paraffin. Then they were evaluated and compared with aqueous suspension and control group. On a large-scale, the sunflower oil-in-water formulation of conidia was sprayed at houses using a hand sprayer.Results: Metarhizium anisopliae IRAN 437C was the most virulent isolate against the brown-banded cockroach, causing 100% mortality in adults at seven days post-exposure. Inoculated bait with this isolate was not enough path­ogenic against the cockroach even at two weeks after treatment. Treated surface with conidia as aqueous suspension or oil-in- water formulation was more effective than the bait formulation against the cockroach caused 39.4–97.2% mortality compared with 2.5% mortality in control group after two days. Spraying the conidia formulated with sun­flower oil was an effective formulation causing 76.1% reduction in the cockroach density on the third day post treatment in the houses.Conclusion: The oil-in-water formulation of M. anisopliae IRAN 437C could be recommended as a promising al­ternative for cockroach control.  

Life style of people and surveillance of management related to cockroaches in Southern Punjab, Pakistan

OpenAIRE

NAEEM, Afifa; JALEEL, Waqar; SAEED, Qamar; ZAKA, Syed Muhammad; SAEED, Shafqat; NAQQASH, Muhammad Nadir; BAKHTAWAR, Marryam; AYUB, Waleed Bin

2014-01-01

Cockroaches are the major household pests which prefer humid areas for habitation i.e. bathrooms, kitchens, sewerage systems etc., where warmth, moisture and food are satisfactory. Cockroaches are responsible for transmitting microorganisms like pathogenic bacteria, virus and fungi. Some examples of common bacterial diseases of human beings transmitted by cockroaches are Pasteurellapestisand bubonic plague; Shigellaalkalescensand dysentery; Staphylococcus aureusand boils and abscesses; Shigel...

Repellent Activity of Apiaceae Plant Essential Oils and their Constituents Against Adult German Cockroaches.

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Lee, Hyo-Rim; Kim, Gil-Hah; Choi, Won-Sil; Park, Il-Kwon

2017-04-01

We evaluated the repellent activity of 12 Apiaceae plant essential oils and their components against male and female adult German cockroaches, Blattella germanica L., to find new natural repellents. Of all the plant essential oils tested, ajowan (Trachyspermum ammi Sprague) and dill (Anethum graveolens L.) essential oils showed the most potent repellent activity against male and female adult German cockroaches. Repellent activities of chemicals already identified in active oils were also investigated. Of the compounds identified, carvacrol, thymol, and R-(-)-carvone showed >80% repellent activity against male and female adult German cockroaches at 2.5 µg/cm2. S-(+)-Carvone, (+)-dihydrocarvone, and terpinen-4-ol showed >70% repellent activity against male and female adult German cockroaches at 10 µg/cm2. Our results indicated that Apiaceae plant essential oils and their constituents have good potential as natural repellents against adult German cockroaches. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Quinuclidine compounds differently act as agonists of Kenyon cell nicotinic acetylcholine receptors and induced distinct effect on insect ganglionic depolarizations.

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Mathé-Allainmat, Monique; Swale, Daniel; Leray, Xavier; Benzidane, Yassine; Lebreton, Jacques; Bloomquist, Jeffrey R; Thany, Steeve H

2013-12-01

We have recently demonstrated that a new quinuclidine benzamide compound named LMA10203 acted as an agonist of insect nicotinic acetylcholine receptors. Its specific pharmacological profile on cockroach dorsal unpaired median neurons (DUM) helped to identify alpha-bungarotoxin-insensitive nAChR2 receptors. In the present study, we tested its effect on cockroach Kenyon cells. We found that it induced an inward current demonstrating that it bounds to nicotinic acetylcholine receptors expressed on Kenyon cells. Interestingly, LMA10203-induced currents were completely blocked by the nicotinic antagonist α-bungarotoxin. We suggested that LMA10203 effect occurred through the activation of α-bungarotoxin-sensitive receptors and did not involve α-bungarotoxin-insensitive nAChR2, previously identified in DUM neurons. In addition, we have synthesized two new compounds, LMA10210 and LMA10211, and compared their effects on Kenyon cells. These compounds were members of the 3-quinuclidinyl benzamide or benzoate families. Interestingly, 1 mM LMA10210 was not able to induce an inward current on Kenyon cells compared to LMA10211. Similarly, we did not find any significant effect of LMA10210 on cockroach ganglionic depolarization, whereas these three compounds were able to induce an effect on the central nervous system of the third instar M. domestica larvae. Our data suggested that these three compounds could bind to distinct cockroach nicotinic acetylcholine receptors.

Effect of thiamethoxam on cockroach locomotor activity is associated with its metabolite clothianidin.

Science.gov (United States)

Benzidane, Yassine; Touinsi, Sarra; Motte, Emilie; Jadas-Hécart, Alain; Communal, Pierre-Yves; Leduc, Lionel; Thany, Steeve H

2010-12-01

In the present study, the effect of thiamethoxam and clothianidin on the locomotor activity of American cockroach, Periplaneta americana (L.), was evaluated. Because it has been proposed that thiamethoxam is metabolised to clothianidin, high-performance liquid chromatography coupled with mass spectrometry was used to evaluate the amount of clothianidin on thiamethoxam-treated cockroaches. One hour after neonicotinoid treatment, the time spent in the open-field-like apparatus significantly increased, suggesting a decrease in locomotor activity. The percentage of cockroaches displaying locomotor activity was significantly reduced 1 h after haemolymph application of 1 nmol g(-1) neonicotinoid, while no significant effect was found after topical and oral administration. However, at 24 and 48 h, all neonicotinoids were able to reduce locomotor activity, depending on their concentrations and the way they were applied. Interestingly, it was found that thiamethoxam was converted to clothianidin 1 h after application, but the amount of clothianidin did not rise proportionately to thiamethoxam, especially after oral administration. The data suggest that the effect of thiamethoxam on cockroach locomotor activity is due in part to clothianidin action because (1) thiamethoxam levels remained persistent 48 h after application and (2) the amount of clothianidin in cockroach tissues was consistent with the toxicity of thiamethoxam. Copyright © 2010 Society of Chemical Industry.

The embodiment of cockroach aggregation behavior in a group of micro-robots.

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Garnier, Simon; Jost, Christian; Gautrais, Jacques; Asadpour, Masoud; Caprari, Gilles; Jeanson, Raphaël; Grimal, Anne; Theraulaz, Guy

2008-01-01

We report the faithful reproduction of the self-organized aggregation behavior of the German cockroach Blattella germanica with a group of robots. We describe the implementation of the biological model provided by Jeanson et al. in Alice robots, and we compare the behaviors of the cockroaches and the robots using the same experimental and analytical methodology. We show that the aggregation behavior of the German cockroach was successfully transferred to the Alice robot despite strong differences between robots and animals at the perceptual, actuatorial, and computational levels. This article highlights some of the major constraints one may encounter during such a work and proposes general principles to ensure that the behavioral model is accurately transferred to the artificial agents.

The prevalence of protozoa in the gut of German cockroaches (Blattella germanica) with special reference to Lophomonas blattarum.

Science.gov (United States)

Martínez-Girón, Rafael; Martínez-Torre, Cristina; van Woerden, Hugo Cornelis

2017-11-01

The German cockroach (Blattella germanica) is a common domestic pest, which produces allergens that have been associated with broncho-pulmonary disease. Various protozoan species have been identified in the intestine of this cockroach and it has been hypothesised that these protozoa, or their proteases, may contribute to the burden of cockroach-associated allergens and adjuvants present in domestic dust. The aim of this study was therefore to determine the prevalence of protozoan species in the intestine of Blattella germanica. German cockroaches were anesthetised and dissected and gut contents are used to produce wet slides for microscopy. Both, Giemsa and Papanicolaou stains were used to confirm correct identification of Lophomonas blattarum. Representatives of four genera of protozoa were identified in 110 cockroaches: Nyctoterus sp. was observed in 91.8% of cases, Gregarina sp. in 64.5%, Amoeba sp. in 25.4% and Lophomonas blattarum in 13.6%. Nyctoterus and Gregarina were statistically significantly more likely to be found in diseased cockroaches compared to Amoeba or Lophomonas. The prevalence of Lophomonas blattarum was similar to that in published studies of a different species of cockroach, Periplaneta americana. Further work is needed to assess the interplay between protozoa, cockroaches and broncho-pulmonary diseases.

Transoceanic Dispersal and Plate Tectonics Shaped Global Cockroach Distributions: Evidence from Mitochondrial Phylogenomics.

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Bourguignon, Thomas; Tang, Qian; Ho, Simon Y W; Juna, Frantisek; Wang, Zongqing; Arab, Daej A; Cameron, Stephen L; Walker, James; Rentz, David; Evans, Theodore A; Lo, Nathan

2017-04-01

Following the acceptance of plate tectonics theory in the latter half of the 20th century, vicariance became the dominant explanation for the distributions of many plant and animal groups. In recent years, however, molecular-clock analyses have challenged a number of well-accepted hypotheses of vicariance. As a widespread group of insects with a fossil record dating back 300 My, cockroaches provide an ideal model for testing hypotheses of vicariance through plate tectonics versus transoceanic dispersal. However, their evolutionary history remains poorly understood, in part due to unresolved relationships among the nine recognized families. Here, we present a phylogenetic estimate of all extant cockroach families, as well as a timescale for their evolution, based on the complete mitochondrial genomes of 119 cockroach species. Divergence dating analyses indicated that the last common ancestor of all extant cockroaches appeared ∼235 Ma, ∼95 My prior to the appearance of fossils that can be assigned to extant families, and before the breakup of Pangaea began. We reconstructed the geographic ranges of ancestral cockroaches and found tentative support for vicariance through plate tectonics within and between several major lineages. We also found evidence of transoceanic dispersal in lineages found across the Australian, Indo-Malayan, African, and Madagascan regions. Our analyses provide evidence that both vicariance and dispersal have played important roles in shaping the distribution and diversity of these insects.

Nest sanitation through defecation: antifungal properties of wood cockroach feces

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Rosengaus, Rebeca B.; Mead, Kerry; Du Comb, William S.; Benson, Ryan W.; Godoy, Veronica G.

2013-11-01

The wood cockroach Cryptocercus punctulatus nests as family units inside decayed wood, a substrate known for its high microbial load. We tested the hypothesis that defecation within their nests, a common occurrence in this species, reduces the probability of fungal development. Conidia of the entomopathogenic fungus, Metarhizium anisopliae, were incubated with crushed feces and subsequently plated on potato dextrose agar. Relative to controls, the viability of fungal conidia was significantly reduced following incubation with feces and was negatively correlated with incubation time. Although the cockroach's hindgut contained abundant β-1,3-glucanase activity, its feces had no detectable enzymatic function. Hence, these enzymes are unlikely the source of the fungistasis. Instead, the antifungal compound(s) of the feces involved heat-sensitive factor(s) of potential microbial origin. When feces were boiled or when they were subjected to ultraviolet radiation and subsequently incubated with conidia, viability was "rescued" and germination rates were similar to those of controls. Filtration experiments indicate that the fungistatic activity of feces results from chemical interference. Because Cryptocercidae cockroaches have been considered appropriate models to make inferences about the factors fostering the evolution of termite sociality, we suggest that nesting in microbe-rich environments likely selected for the coupling of intranest defecation and feces fungistasis in the common ancestor of wood cockroaches and termites. This might in turn have served as a preadaptation that prevented mycosis as these phylogenetically related taxa diverged and evolved respectively into subsocial and eusocial organizations.

Grooming behavior in American cockroach is affected by novelty and odor.

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Zhukovskaya, Marianna I

2014-01-01

The main features of grooming behavior are amazingly similar among arthropods and land vertebrates and serve the same needs. A particular pattern of cleaning movements in cockroaches shows cephalo-caudal progression. Grooming sequences become longer after adaptation to the new setting. Novelty related changes in grooming are recognized as a form of displacement behavior. Statistical analysis of behavior revealed that antennal grooming in American cockroach, Periplaneta americana L., was significantly enhanced in the presence of odor.

Diet shapes the gut microbiota of the omnivorous cockroach Blattella germanica.

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Pérez-Cobas, Ana Elena; Maiques, Elisa; Angelova, Alexandra; Carrasco, Purificación; Moya, Andrés; Latorre, Amparo

2015-04-01

The gut microbiota of insects contributes positively to the physiology of its host mainly by participating in food digestion, protecting against pathogens, or provisioning vitamins or amino acids, but the dynamics of this complex ecosystem is not well understood so far. In this study, we have characterized the gut microbiota of the omnivorous cockroach Blattella germanica by pyrosequencing the hypervariable regions V1-V3 of the 16S rRNA gene of the whole bacterial community. Three diets differing in the protein content (0, 24 and 50%) were tested at two time points in lab-reared individuals. In addition, the gut microbiota of wild adult cockroaches was also analyzed. In contrast to the high microbial richness described on the studied samples, only few species are shared by wild and lab-reared cockroaches, constituting the bacterial core in the gut of B. germanica. Overall, we found that the gut microbiota of B. germanica is highly dynamic as the bacterial composition was reassembled in a diet-specific manner over a short time span, with no-protein diet promoting high diversity, although the highest diversity was found in the wild cockroaches analyzed. We discuss how the flexibility of the gut microbiota is probably due to its omnivorous life style and varied diets. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Students' Knowledge about the Internal Structure of Mice and Cockroaches in Their Environment

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Kilic, Selda

2013-01-01

The aim of this study is to determine 9th class students knowledge about the internal structures of mice and cockroaches using drawings. Drawings of 122 students from the 9th class of a high school in the center of Konya about the internal structures of mice and cockroaches have been analyzed. Drawings were analyzed independently by two…

Reversible brain inactivation induces discontinuous gas exchange in cockroaches.

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Matthews, Philip G D; White, Craig R

2013-06-01

Many insects at rest breathe discontinuously, alternating between brief bouts of gas exchange and extended periods of breath-holding. The association between discontinuous gas exchange cycles (DGCs) and inactivity has long been recognised, leading to speculation that DGCs lie at one end of a continuum of gas exchange patterns, from continuous to discontinuous, linked to metabolic rate (MR). However, the neural hypothesis posits that it is the downregulation of brain activity and a change in the neural control of gas exchange, rather than low MR per se, which is responsible for the emergence of DGCs during inactivity. To test this, Nauphoeta cinerea cockroaches had their brains inactivated by applying a Peltier-chilled cold probe to the head. Once brain temperature fell to 8°C, cockroaches switched from a continuous to a discontinuous breathing pattern. Re-warming the brain abolished the DGC and re-established a continuous breathing pattern. Chilling the brain did not significantly reduce the cockroaches' MR and there was no association between the gas exchange pattern displayed by the insect and its MR. This demonstrates that DGCs can arise due to a decrease in brain activity and a change in the underlying regulation of gas exchange, and are not necessarily a simple consequence of low respiratory demand.

Isolation of Intestinal Parasites of Public Health Importance from Cockroaches (Blattella germanica) in Jimma Town, Southwestern Ethiopia.

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Hamu, Haji; Debalke, Serkadis; Zemene, Endalew; Birlie, Belay; Mekonnen, Zeleke; Yewhalaw, Delenasaw

2014-01-01

Cockroaches are claimed to be mechanical transmitters of disease causing microorganisms such as intestinal parasites, bacteria, fungi, and viruses. This study assessed the potential of the German cockroach Blattella germanica in the mechanical transmission of intestinal parasites of public health importance. A total of 2010 cockroaches were collected from 404 households in Jimma Town, southwestern Ethiopia. All the collected cockroaches were identified to species as B. germanica. The contents of their gut and external body parts were examined for the presence of intestinal parasites. Overall, 152 (75.6%) of the 210 batches were found to harbor at least one species of human intestinal parasite. Ascaris lumbricoides, Trichuris trichiura, Taenia spp, Strongyloides-like parasite, Entamoeba histolytica/dispar/moshkovski, Giardia duodenalis and Balantidium coli were detected from gut contents. Moreover, parasites were also isolated from the external surface in 22 (10.95%) of the batches. There was significant difference in parasite carriage rate of the cockroaches among the study sites (P = 0.013). In conclusion, B. germanica was found to harbor intestinal parasites of public health importance. Hence, awareness on the potential role of cockroaches in the mechanical transmission of human intestinal parasites needs to be created. Moreover, further identification of the Strongyloides-like worm is required using molecular diagnostics.

Isolation of Intestinal Parasites of Public Health Importance from Cockroaches (Blattella germanica in Jimma Town, Southwestern Ethiopia

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Haji Hamu

2014-01-01

Full Text Available Cockroaches are claimed to be mechanical transmitters of disease causing microorganisms such as intestinal parasites, bacteria, fungi, and viruses. This study assessed the potential of the German cockroach Blattella germanica in the mechanical transmission of intestinal parasites of public health importance. A total of 2010 cockroaches were collected from 404 households in Jimma Town, southwestern Ethiopia. All the collected cockroaches were identified to species as B. germanica. The contents of their gut and external body parts were examined for the presence of intestinal parasites. Overall, 152 (75.6% of the 210 batches were found to harbor at least one species of human intestinal parasite. Ascaris lumbricoides, Trichuris trichiura, Taenia spp, Strongyloides-like parasite, Entamoeba histolytica/dispar/moshkovski, Giardia duodenalis and Balantidium coli were detected from gut contents. Moreover, parasites were also isolated from the external surface in 22 (10.95% of the batches. There was significant difference in parasite carriage rate of the cockroaches among the study sites (P=0.013. In conclusion, B. germanica was found to harbor intestinal parasites of public health importance. Hence, awareness on the potential role of cockroaches in the mechanical transmission of human intestinal parasites needs to be created. Moreover, further identification of the Strongyloides-like worm is required using molecular diagnostics.

Mixing compatibilities of Aspergillus and American cockroach allergens with other high-protease fungal and insect extracts.

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Grier, Thomas J; Hall, Dawn M; Duncan, Elizabeth A; Coyne, Terrance C

2015-03-01

Recent studies have shown that Alternaria and German cockroach allergens can be degraded by endogenous proteases from other insect and fungal extracts when combined for immunotherapy, but data supporting the compatibilities of other high-protease products in comparable mixtures have not been reported. To assess the stabilities and compatibilities of Aspergillus fumigatus and American cockroach allergens after mixing with protease-rich extracts from other insects or fungi at concentrations similar to those recommended for subcutaneous immunotherapy. Mixtures containing A fumigatus, American cockroach, and other fungal or insect extracts were evaluated by quantitative (enzyme-linked immunosorbent assays) and qualitative (immunoblotting) methods. Test mixtures and control samples at 10% to 50% glycerin concentrations were analyzed after storage for up to 12 months at 2°C to 8°C. Moderate to high recoveries of Aspergillus extract activities were retained in control samples and extract mixtures under all conditions examined. American cockroach extract controls were partly degraded at 10% to 25% glycerin, and cockroach allergen compatibilities were decreased significantly in mixtures with several fungal extracts at 25% glycerin. Mixing with other insects did not compromise the stability of American cockroach allergens at 25% to 50% glycerin. Aspergillus extracts exhibited favorable stabilities after mixing with other high-protease products. American cockroach extract potencies were unstable in less than 50% glycerin, even in the absence of other protease-containing allergens, and were destabilized in mixtures with several fungal extracts. Addition of fungal and insect extracts to separate treatment vials or preparation of fungal-insect mixtures at elevated glycerin concentrations might be necessary to produce compatible patient formulations for allergen immunotherapy injections. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier

Synanthropic Cockroaches (Blattidae: Periplaneta spp.) Harbor Pathogenic Leptospira in Colombia.

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Gonzalez-Astudillo, Viviana; Bustamante-Rengifo, Javier A; Bonilla, Álvaro; Lehmicke, Anna Joy J; Castillo, Andrés; Astudillo-Hernández, Miryam

2016-01-01

Leptospirosis cases in Colombia are typically linked to peridomestic rodents; however, empirical data suggest that Leptospira-infected patients with no apparent exposure to these reservoirs are common. Cockroaches (Periplaneta spp.) have equal or greater interaction with humans than rodents, yet their potential role as carriers of Leptospira has not been assessed. We determined if pathogenic Leptospira is harbored by Periplaneta spp. in Cali (Colombia) and the variables influencing this relationship. Fifty-nine cockroaches were captured from seven sites and DNA was extracted from the body surface and digestive tract for a multiplex polymerase chain reaction, targeting genes secY and flaB. Logistic regression models and proportion tests showed a higher likelihood for Leptospira to be isolated from body surfaces (P > 0.001) and from individuals inside houses (six times more likely). These findings are the first to demonstrate an association between Periplaneta spp. and Leptospira, suggesting the need to investigate the potential for cockroaches to serve as reservoirs or transport hosts for Leptospira. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Horizontal transfer of bait in the German cockroach: indoxacarb causes secondary and tertiary mortality.

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Buczkowski, Grzegorz; Scherer, Clay W; Bennett, Gary W

2008-06-01

Horizontal transfer of indoxacarb in the German cockroach, Blattella germanica (L.), was examined under laboratory conditions. Results show that a single bait-fed adult cockroach (i.e., the donor) transferred indoxacarb to numerous primary recipients (secondary mortality),which then became secondary donors. These recipients subsequently became donors to other cockroaches and caused significant mortality in other members of the aggregation, resulting in tertiary kill. Indoxacarb was effectively transferred among adult cockroaches and resulted in significant secondary mortality. When adult males served as donors and vectored the insecticide to adult males, the donor:recipient ratio affected the mortality of the recipients and the rate of secondary mortality increased with increasing the ratio of donors to recipients. Furthermore, secondary mortality in the untreated cockroaches was significantly affected by the freshness of excretions from the donors, the presence of alternative food, and the duration of contact between the donors and the recipients. Ingested indoxacarb was most effectively translocated when the recipients interacted with freshly symptomatic donors in the absence of alternative food. The transfer of indoxacarb continued beyond secondary mortality and resulted in significant tertiary mortality. Excretions from a single bait-fed adult killed 38/50 (76%) nymphs within 72 h. The dead nymphs then vectored indoxacarb to 20 adult males and killed 16/20 (81%) recipients within 72 h. Behavioral mechanisms involved in the horizontal transfer of indoxacarb may include: contact with excretions, necrophagy, emetophagy, and ingestion of other excretions that originate from the donors.

Evaluation of Five Local Formulated Insecticides against German Cockroach (Blattella germanica L. in Southern Iran

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M Shahi

2008-06-01

Full Text Available Background: The German cockroach, Blattella germanica L., is a serious household and public health pest worldwide. Con­trol of this species has been very difficult to achieve. Toxicity of cypermethrin EC10%, deltamethrin EC5%, diazi­non EC0.5%, lambda-cyhalothrin EC5% and Negon® (permethrin+propoxur oil liquid1% commercial for­mula­tions were investigated against adult males of German cockroaches collected from four hospitals of Bandar Abbas City, southern Iran, during 2006. These insecticides have been used for cockroach con­trol in this city.Methods: The tests were carried out only on males by the glass jar contact method recommended by the WHO.Results: Maximum mortality rates of 20, 35, 90, and 100% were obtained after one hour contact to label-recom­mended doses of cypermethrin, deltamethrin, lambad-cyhalothrin, diazinon and permethrin+propoxur insecti­cides, respectively. KT50 results were different from 5.68 min for permethrin+propoxur mixture to 240.37 min for cyper­methrin. German cockroach showed < 80 per cent mortality using three pyrethroid insecticides.Conclusion: It seems that the label-recommended concentrations of these insecticides were wrong and lower than WHO advised for cockroach control. For monitoring of resistance it is recommended to do more tests using the pure ac­tive ingredient of these insecticides.

Pycnoscelus surinamensis cockroach gut microbiota respond consistently to a fungal diet without mirroring those of fungus-farming termites.

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Callum Richards

Full Text Available The gut microbiotas of cockroaches and termites play important roles in the symbiotic digestion of dietary components, such as lignocellulose. Diet has been proposed as a primary determinant of community structure within the gut, acting as a selection force to shape the diversity observed within this "bioreactor", and as a key factor for the divergence of the termite gut microbiota from the omnivorous cockroach ancestor. The gut microbiota in most termites supports primarily the breakdown of lignocellulose, but the fungus-farming sub-family of higher termites has become similar in gut microbiota to the ancestral omnivorous cockroaches. To assess the importance of a fungus diet as a driver of community structure, we compare community compositions in the guts of experimentally manipulated Pycnoscelus surinamensis cockroaches fed on fungus cultivated by fungus-farming termites. MiSeq amplicon analysis of gut microbiotas from 49 gut samples showed a step-wise gradient pattern in community similarity that correlated with an increase in the proportion of fungal material provided to the cockroaches. Comparison of the taxonomic composition of manipulated communities to that of gut communities of a fungus-feeding termite species showed that although some bacteria OTUs shared by P. surinamensis and the farming termites increased in the guts of cockroaches on a fungal diet, cockroach communities remained distinct from those of termites. These results demonstrate that a fungal diet can play a role in structuring gut community composition, but at the same time exemplifies how original community compositions constrain the magnitude of such change.

The Use of Genetic Mechanisms and Behavioral Characteristics to Control Natural Populations of the German Cockroach.

Science.gov (United States)

1981-03-01

release of sterile males into natural populations of the German cockroach. Submitted to Entomologia exp. & Appl. Feb., 1981. A first draft was...populations of the German cockroach. Subm. Entomologia Exp. & Appl. Feb., 1981. aEight other publications of earlier research on this Contract have

Cockroaches traverse crevices, crawl rapidly in confined spaces, and inspire a soft, legged robot

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Jayaram, Kaushik; Full, Robert J.

2016-01-01

Jointed exoskeletons permit rapid appendage-driven locomotion but retain the soft-bodied, shape-changing ability to explore confined environments. We challenged cockroaches with horizontal crevices smaller than a quarter of their standing body height. Cockroaches rapidly traversed crevices in 300–800 ms by compressing their body 40–60%. High-speed videography revealed crevice negotiation to be a complex, discontinuous maneuver. After traversing horizontal crevices to enter a vertically confined space, cockroaches crawled at velocities approaching 60 cm⋅s−1, despite body compression and postural changes. Running velocity, stride length, and stride period only decreased at the smallest crevice height (4 mm), whereas slipping and the probability of zigzag paths increased. To explain confined-space running performance limits, we altered ceiling and ground friction. Increased ceiling friction decreased velocity by decreasing stride length and increasing slipping. Increased ground friction resulted in velocity and stride length attaining a maximum at intermediate friction levels. These data support a model of an unexplored mode of locomotion—“body-friction legged crawling” with body drag, friction-dominated leg thrust, but no media flow as in air, water, or sand. To define the limits of body compression in confined spaces, we conducted dynamic compressive cycle tests on living animals. Exoskeletal strength allowed cockroaches to withstand forces 300 times body weight when traversing the smallest crevices and up to nearly 900 times body weight without injury. Cockroach exoskeletons provided biological inspiration for the manufacture of an origami-style, soft, legged robot that can locomote rapidly in both open and confined spaces. PMID:26858443

Antibiotics susceptibility patterns of bacteria isolated from American and German cockroaches as potential vectors of microbial pathogens in hospitals

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Mohammad Reza Fakoorziba

2014-09-01

Full Text Available Objective: To identify the cockroach species, their bacterial flora and antibiotics susceptibility patterns of these bacteria in Shiraz. Methods: In the present descriptive study, only two species of cockroaches were recognized. The washing solutions from the digestion systems and surfaces of 156 American and German cockroaches were cultured. The latter was found to be the commonest (89.7% in all places. Results: Overall, 18 species of bacteria were isolated and identified by standard culture methods. The most frequent bacterium isolated from both species of cockroaches in all places was Pseudomonas (41.7%. The second and third commonest bacteria were Enterobacter (39.7% and Klebsiella (32.7%, respectively. Conclusions: The antibiogram profiles showed full (100% resistance of Klebsiella, Citrobacter, Acinetobacter and Proteus to amoxicillin and ampicillin at both hospitals, while Pseudomonas showed resistance (95.7% to cephalothin. Thus it is concluded that German and American cockroaches carry multidrug resistant bacteria in two hospitals which raises alarm for stricter control measures.

Energetic Cost of Subacute Chlorpyrifos Intoxication in the German Cockroach (Dictyoptera: Blattellidae)

DEFF Research Database (Denmark)

Nielsen, Søren Achim; Jensen, Karl-Martin Vagn; Kristensen, Michael

2006-01-01

The energetic cost of a sublethal treatment with chlorpyrifos was estimated by use of direct microcalorimetry to measure metabolic heat in susceptible and resistant strains of the German cockroach Blattella germanica L. Moreover, one of the detoxifcation enzyme systems known to be involved...... in detoxifcation of chlorpyrifos, glutathione-S-transferase, was measured. Individual cockroaches were exposed for 20 min on a glass-surfaces treated with 1.14 ...  g/cm2 of chlorpyrifos. There was no difference in glutathione-S-transferase activity of susceptible or resistant strains after the treatment. The heat...

Resonance – Journal of Science Education | Indian Academy of ...

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 8. Lipophorin Receptor: The Insect Lipoprotein Receptor. G Ravikumar N B Vijayaprakash. General Article Volume 18 Issue 8 August 2013 pp 748-755. Fulltext. Click here to view fulltext PDF. Permanent link:

Design and Implementation of Markerless Augmented Reality Application for Cockroach Phobia Therapy Using Adaptive Threshold

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Fiandra Fatharany

2017-01-01

Full Text Available Augmented reality (AR technology is useful for treating several psychological problems, including phobias such as fear of flying, agoraphobia, claustrophobia, and phobia to insects and small animals. However, the currently existing applications for therapy of cockroach phobia that uses AR technology are still very dependent towards the presence of markers, which might lessen the feeling of being in an actual scenario from everyday lives. In this paper, we created a system that is able to use everyday things as a replacement for markers for phobia therapy for cockroach. There are five main processes: getting the live streaming feed from camera, preprocessing, extracting the center point of the objects, tracking the marker-substitute objects, and lastly, instantiating cockroaches randomly after user lifts the objects according to the number and mode of the cockroaches, whether it is moving or not, that are predetermined by the user. The evaluation in this paper includes eight participants that are carefully selected based on their Fear of Spiders Questionnaire (FSQ score that is translated into Indonesian and modified to accommodate cockroaches instead of spiders. The results is that the system can induce anxiety level on participants with the highest score of 10, which is the highest score in Standard Unit of Discomfort scale (SUDs. While the presence and reality judgment of this paper has the highest score of 7 which is also the highest score in Slater-Usoh-Steed Questionnaire (SUS.

Pyrethroid resistance and cross-resistance in the German cockroach, Blattella germanica (L).

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Wei, Y; Appel, A G; Moar, W J; Liu, N

2001-11-01

A German cockroach (Blatella germanica (L)) strain, Apyr-R, was collected from Opelika, Alabama after control failures with pyrethroid insecticides. Levels of resistance to permethrin and deltamethrin in Apyr-R (97- and 480-fold, respectively, compared with a susceptible strain, ACY) were partially or mostly suppressed by piperonyl butoxide (PBO) and S,S,S,-tributylphosphorotrithioate (DEF), suggesting that P450 monooxygenases and hydrolases are involved in resistance to these two pyrethroids in Apyr-R. However, incomplete suppression of pyrethroid resistance with PBO and DEF implies that one or more additional mechanisms are involved in resistance. Injection, compared with topical application, resulted in 43- and 48-fold increases in toxicity of permethrin in ACY and Apyr-R, respectively. Similarly, injection increased the toxicity of deltamethrin 27-fold in ACY and 28-fold in Apyr-R. These data indicate that cuticular penetration is one of the obstacles for the effectiveness of pyrethroids against German cockroaches. However, injection did not change the levels of resistance to either permethrin or deltamethrin, suggesting that a decrease in the rate of cuticular penetration may not play an important role in pyrethroid resistance in Apyr-R. Apyr-R showed cross-resistance to imidacloprid, with a resistance ratio of 10. PBO treatment resulted in no significant change in the toxicity of imidacloprid, implying that P450 monooxygenase-mediated detoxication is not the mechanism responsible for cross-resistance. Apyr-R showed no cross-resistance to spinosad, although spinosad had relatively low toxicity to German cockroaches compared with other insecticides tested in this study. This result further confirmed that the mode of action of spinosad to insects is unique. Fipronil, a relatively new insecticide, was highly toxic to German cockroaches, and the multi-resistance mechanisms in Apyr-R did not confer significant cross-resistance to this compound. Thus, we propose

Selected food-borne parasites associated with cockroaches and ...

African Journals Online (AJOL)

Of these, 20 (62.5%) were protozoa and 12 (37.5%) were helminthes from the houseflies while 19 (54.3%) were protozoa and 16 (45.7%) were helminthes from the cockroaches. The protozoa that were identified include; cysts of Balantidium coli, cysts of Entamoeba coli, Entamoeba Histolytica and Endolimax nana. Also ...

Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

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Li, Guangye; Zhang, Dingguo

2016-01-01

An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

N B Vijayaprakash

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education. N B Vijayaprakash. Articles written in Resonance – Journal of Science Education. Volume 18 Issue 8 August 2013 pp 748-755 General Article. Lipophorin Receptor: The Insect Lipoprotein Receptor · G Ravikumar N B Vijayaprakash · More Details Fulltext PDF ...

Symbiotic essential amino acids provisioning in the American cockroach, Periplaneta americana (Linnaeus) under various dietary conditions.

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Ayayee, Paul A; Larsen, Thomas; Sabree, Zakee

2016-01-01

Insect gut microbes have been shown to provide nutrients such as essential amino acids (EAAs) to their hosts. How this symbiotic nutrient provisioning tracks with the host's demand is not well understood. In this study, we investigated microbial essential amino acid (EAA) provisioning in omnivorous American cockroaches (Periplaneta americana), fed low-quality (LQD) and comparatively higher-quality dog food (DF) diets using carbon stable isotope ratios of EAAs (δ (13)CEAA). We assessed non-dietary EAA input, quantified as isotopic offsets (Δ(13)C) between cockroach (δ (13)CCockroach EAA) and dietary (δ (13)CDietary EAA) EAAs, and subsequently determined biosynthetic origins of non-dietary EAAs in cockroaches using (13)C-fingerprinting with dietary and representative bacterial and fungal δ (13)CEAA. Investigation of biosynthetic origins of de novo non-dietary EAAs indicated bacterial origins of EAA in cockroach appendage samples, and a mixture of fungal and bacterial EAA origins in gut filtrate samples for both LQD and DF-fed groups. We attribute the bacteria-derived EAAs in cockroach appendages to provisioning by the fat body residing obligate endosymbiont, Blattabacterium and gut-residing bacteria. The mixed signatures of gut filtrate samples are attributed to the presence of unassimilated dietary, as well as gut microbial (bacterial and fungal) EAAs. This study highlights the potential impacts of dietary quality on symbiotic EAA provisioning and the need for further studies investigating the interplay between host EAA demands, host dietary quality and symbiotic EAA provisioning in response to dietary sufficiency or deficiency.

Toxicity of Cypermethrin and Chlorpyrifos Against German Cockroach [ Blattella germanica (Blattaria: Blattellidae)] Strains from Hamadan, Iran.

Science.gov (United States)

Nazari, Mansour; Motlagh, Behrouz Alipourian; Nasirian, Hassan

German cockroach has relatively short life cycle and reproduce rapidly. It is the most common medically and public health pest. As a result, it is essential to combat this pest. Cypermethrin and chlorpyrifos are used by private companies in Hamadan to control Blattella germanica. It seems necessary to determine its susceptibility levels to these insecticides. The aim of this study was to determine the susceptibility levels of B. germanica strains to cypermethrin and chlorpyrifos in Hamadan. In this study, the German cockroach strains were collected from two hospitals (Fatemiyeh and Atiyeh) in Hamadan and transfered to the insectarium. The cockroach strains were reared under the same laboratory condition. Then their sensitivity levels were considered to 1, 2, 4, 8 and 16 mg m -2 for cypermethrin and 0.82, 1.65, 3.31, 6.63, 9.945 and 13.26 mg m -2 for chlorpyrifos using surface contact method. Results based on insecticide treated doses, B. germanica strains showed different percent mortality to the insecticides ranged from 13.3-100. The LD 50 and LD 90 and regression lines of the treated insecticides against German cockroach strains indicate that Fatemiyeh Hospital strain is more susceptible to the treated insecticides than Atiyeh Hospital strain. The LD 50 and LD 90 of chlorpyrifos are also lower than cypermethrin, indicated that chlorpyrifos is more effective than cypermethrin against German cockroach. As the slopes of the regression lines are observed mild in this study indicate that the population of the cockroach strains is very heterogeneous. It can be a symbol of insecticides resistance to cypermethrin and chlorpyrifos. As chlorpyrifos and cypermethrin insecticides are also used for residual spraying by private companies and the doses which provide more than 90% mortality are below the WHO recommended insecticide doses. Therefore, chlorpyrifos and cypermethrin insecticides can be used for B. germanica control in Hamadan within regular monitoring and preventive

Effectiveness of an integrated pest management intervention in controlling cockroaches, mice, and allergens in New York City public housing.

Science.gov (United States)

Kass, Daniel; McKelvey, Wendy; Carlton, Elizabeth; Hernandez, Marta; Chew, Ginger; Nagle, Sean; Garfinkel, Robin; Clarke, Brian; Tiven, Julius; Espino, Christian; Evans, David

2009-08-01

Cockroaches and mice, which are common in urban homes, are sources of allergens capable of triggering asthma symptoms. Traditional pest control involves the use of scheduled applications of pesticides by professionals as well as pesticide use by residents. In contrast, integrated pest management (IPM) involves sanitation, building maintenance, and limited use of least toxic pesticides. We implemented and evaluated IPM compared with traditional practice for its impact on pests, allergens, pesticide use, and resident satisfaction in a large urban public housing authority. We assigned IPM or control status to 13 buildings in five housing developments, and evaluated conditions at baseline, 3 months, and 6 months in 280 apartments in Brooklyn and Manhattan, in New York City (New York). We measured cockroach and mouse populations, collected cockroach and mouse urinary protein allergens in dust, and interviewed residents. All statistical models controlled for baseline levels of pests or allergens. Compared with controls, apartments receiving IPM had significantly lower counts of cockroaches at 3 months and greater success in reducing or sustaining low counts of cockroaches at both 3 and 6 months. IPM was associated with lower cockroach allergen levels in kitchens at 3 months and in beds and kitchens at 6 months. Pesticide use was reduced in IPM relative to control apartments. Residents of IPM apartments also rated building services more positively. In contrast to previous IPM studies, which involved extensive cleaning, repeat visits, and often extensive resident education, we found that an easily replicable single IPM visit was more effective than the regular application of pesticides alone in managing pests and their consequences.

Insecticidal and acetylcholine esterase inhibition activity of Asteraceae plant essential oils and their constituents against adults of the German cockroach (Blattella germanica).

Science.gov (United States)

Yeom, Hwa-Jeong; Jung, Chan-Sik; Kang, Jaesoon; Kim, Junheon; Lee, Jae-Hyeon; Kim, Dong-Soo; Kim, Hyun-Seok; Park, Pil-Sun; Kang, Kyu-Suk; Park, Il-Kwon

2015-03-04

The fumigant and contact toxicities of 16 Asteraceae plant essential oils and their constituents against adult male and female Blattella germanica were examined. In a fumigant toxicity test, tarragon oil exhibited 100% and 90% fumigant toxicity against adult male German cockroaches at 5 and 2.5 mg/filter paper, respectively. Fumigant toxicities of Artemisia arborescens and santolina oils against adult male German cockroaches were 100% at 20 mg/filter paper, but were reduced to 60% and 22.5% at 10 mg/filter paper, respectively. In contact toxicity tests, tarragon and santolina oils showed potent insecticidal activity against adult male German cockroaches. Components of active oils were analyzed using gas chromatography, gas chromatography-mass spectrometry, or nuclear magnetic resonance spectrometer. Among the identified compounds from active essential oils, estragole demonstrated potent fumigant and contact toxicity against adult German cockroaches. β-Phellandrene exhibited inhibition of male and female German cockroach acetylcholinesterase activity with IC50 values of 0.30 and 0.28 mg/mL, respectively.

The First Report of Drug Resistant Bacteria Isolated from the Brown-Banded Cockroach, Supella longipalpa, in Ahvaz, South-western Iran.

Directory of Open Access Journals (Sweden)

Babak Vazirianzadeh

2014-06-01

Full Text Available The brown-banded cockroach, Supella longipalpa is known as a carrier of pathogenic bacteria in urban environments, but its role is not well documented regarding the carriage of antibiotic-resistant pathogenic bacteria in Iran. The aim of this study was to determine the resistance bacteria isolated from the brown-banded cockroach in Ahvaz, south west of Iran.Totally 39 cockroaches were collected from kitchen area of houses and identified. All specimens were cultured to isolate the bacterial agents on blood agar and MacConky agar media. The microorganisms were identified using necessary differential and biochemical tests. Antimicrobial susceptibility tests were performed for isolated organisms by Kirby-Bauer's disk diffusion according to NCLI guideline, using 18 antibiotics.From the 39 collected S. langipalpa, 179 bacterial agents were isolated, 92 of alimentary ducts and 87 of external body surfaces. Isolated bacteria from cockroaches were identified as Enterobacter spp., Klebsiella spp., Citrobacter spp., Escherichia coli, Salmonella spp., Proteus spp., coagulase negative staphylococci, Serratia marcescens, Staphylococcus aureus, and Bacillus species. The pattern resistance rates were determined for gram negative bacilli and gram positive cocci regarding 18 antibiotics.The brown-banded cockroach can be involved in the spread of drug resistant bacteria and increases the possibility of contacting human environment to drug resistant bacteria. Therefore, the potential of removing this insect should be improved. This is the first original report of drug resistant bacteria isolated from the brown-banded cockroach of Iran.

Pycnoscelus surinamensis cockroach gut microbiota respond consistently to a fungal diet without mirroring those of fungus-farming termites

DEFF Research Database (Denmark)

Richards, Callum; Otani, Saria; Mikaelyan, Aram

2017-01-01

The gut microbiotas of cockroaches and termites play important roles in the symbiotic digestion of dietary components, such as lignocellulose. Diet has been proposed as a primary determinant of community structure within the gut, acting as a selection force to shape the diversity observed within......-feeding termite species showed that although some bacteria OTUs shared by P. surinamensis and the farming termites increased in the guts of cockroaches on a fungal diet, cockroach communities remained distinct from those of termites. These results demonstrate that a fungal diet can play a role in structuring gut...

Origin and extent of resistance to fipronil in the German cockroach, Blattella germanica (L.) (Dictyoptera: Blattellidae).

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Holbrook, Glenn L; Roebuck, Jamie; Moore, Clyde B; Waldvogel, Michael G; Schal, Coby

2003-10-01

Fipronil, a phenylpyrazole insecticide, was made available in 1999 in bait formulations for use against the German cockroach, Blattella germanica (L.). We have investigated resistance to fipronil in the descendants of cockroaches collected just before, or contemporaneously with, the introduction of fipronil baits. Cockroaches were obtained in two types of settings: homes that either had or had not been serviced by a pest management professional while occupied by their current residents. Thorough inspections by us turned up no evidence that fipronil had been used in any of the homes, and in addition, no residents claimed to have used baits containing fipronil. Resistance to fipronil was detected by topically dosing adult males with the LC99 of fipronil, the value of which was determined in a dose-response assay with males of an insecticide-susceptible strain. Fewer than 99 of 100 males of all field-collected strains died within 72 h of being treated. Moreover, substantial numbers of males survived doses three and 10-fold greater than the LC99. Regression analysis showed that 67% of the variation in the percentage of males that died after being treated with fipronil was explained by a linear relationship with the percentage that died after being treated with dieldrin. Therefore, it appears that resistance to fipronil in German cockroaches--whose ancestors had never been exposed to it--is attributable to enduring resistance to the cyclodienes, which were formerly used for cockroach control and have a similar mode of action as fipronil. Lastly, we found that insects resistant to topically administered fipronil were likewise resistant, and to a similar degree, to ingested fipronil.

Inhibition of PaCaMKII-E isoform in the dorsal unpaired median neurosecretory cells of cockroach reduces nicotine- and clothianidin-induced currents.

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List, Olivier; Calas-List, Delphine; Taillebois, Emiliane; Juchaux, Marjorie; Heuland, Emilie; Thany, Steeve H

2014-08-01

Cellular responses to Ca(2+) require intermediary proteins such as calcium/calmodulin-dependent protein kinase II (CaMKII), which transduces the signal into downstream effects. We recently demonstrated that the cockroach genome encodes five different CaMKII isoforms, and only PaCaMKII-E isoform is specifically expressed in the dorsal unpaired median neurosecretory cells. In the present study, using antisense oligonucleotides, we demonstrated that PaCaMKII-E isoform inhibition reduced nicotine-induced currents through α-bungarotoxin-sensitive and -insensitive nicotinic acetylcholine receptor subtypes. Specifically, PaCaMKII-E isoform is sufficient to repress nicotinic current amplitudes as a result of its depression by antisense oligonucleotides. Similar results were found using the neonicotinoid insecticide clothianidin, which acted as a full agonist of dorsal unpaired median neuron nicotinic acetylcholine receptors. Clothianidin current amplitudes are strongly reduced under bath application of PaCaMKII-E antisense oligonucleotides but no significant results are found with α-bungarotoxin co-applied, demonstrating that CaMKII-E isoform affects nicotine currents through α-bungarotoxin-sensitive and -insensitive receptor subtypes whereas clothianidin currents are reduced via α-bungarotoxin-insensitive receptors. In addition, we found that intracellular calcium increase induced by nicotine and clothianidin were reduced by PaCaMKII-E antisense oligonucleotides, demonstrating that intracellular calcium increase induced by nicotine and clothianidin are affected by PaCaMKII-E inhibition. Cellular responses to Ca(2+) require intermediary proteins such as calcium/calmodulin-dependent protein kinase II (CaMKII). We recently demonstrated that the cockroach genome encodes five different CaMKII isoforms and only PaCaMKII-E isoform was specifically expressed in the dorsal unpaired median neurosecretory cells. Here we show that specific inhibition of PaCaMKII-E isoform is

New predatory cockroaches (Insecta: Blattaria: Manipulatoridae fam.n.) from the Upper Cretaceous Myanmar amber

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Vršanský, Peter; Bechly, Günter

2015-04-01

We describe a new extinct lineage Manipulatoridae (new family) of cockroaches from the Upper Cretaceous (Cenomanian) amber of Myanmar. Manipulator modificaputis gen. et sp. n. is a morphologically unique extinct cockroach that represents the first (of a total of 29 known worldwide) cockroach family reported exclusively from the Myanmar amber. This family represents an early side branch of the stem group of Mantodea (most probably a sister group of Eadiidae within Blattaria/Corydioidea) because it has some synapomorphies with the Mantodea (including the stem group and Eadiidae). This family also retains symplesiomorphies that exclude a position in the crown group, and furthermore has unique autapomorphies that exclude a position as a direct ancestor of Mantodea. The unique adaptations such as strongly elongated extremities and freely movable head on a long neck suggest that these animals were pursuit predators. Five additional specimens (including two immatures) reported from the Myanmar amber suggest that this group was relatively rare but belonged to the indigenous and autochthonous inhabitants of the ancient amber forest of the Myanmar region.

Arthromitus (Bacillus cereus) symbionts in the cockroach Blaberus giganteus: dietary influences on bacterial development and population density

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Feinberg, L.; Jorgensen, J.; Haselton, A.; Pitt, A.; Rudner, R.; Margulis, L.

1999-01-01

The filamentous spore-forming bacterium Arthromitus, discovered in termites, millipedes, sow bugs and other soil-dwelling arthropods by Leidy (1850), is the intestinal stage of Bacillus cereus. We extend the range of Arthromitus habitats to include the hindgut of Blaberus giganteus, the large tropical American cockroach. The occurrence and morphology of the intestinal form of the bacillus were compared in individual cockroaches (n=24) placed on four different diet regimes: diurnally maintained insects fed (1) dog food, (2) soy protein only, (3)purified cellulose only, and (4) a dog food-fed group maintained in continuous darkness. Food quality exerted strong influence on population densities and developmental stages of the filamentous bacterium and on fecal pellet composition. The most dramatic rise in Arthromitus populations, defined as the spore-forming filament intestinal stage, occurred in adult cockroaches kept in the dark on a dog food diet. Limited intake of cellulose or protein alone reduced both the frequency of Arthromitus filaments and the rate of weight gain of the insects. Spores isolated from termites, sow bugs, cockroaches and moths, grown on various hard surfaces display a branching mobility and resistance to antibiotics characteristic to group I Bacilli whose members include B. cereus, B. circulans, B. alvei and B. macerans. DNA isolated from pure cultures of these bacilli taken from the guts of Blaberus giganteus (cockroach), Junonia coenia (moth), Porcellio scaber (sow bug) and Cryptotermes brevis (termite) and subjected to Southern hybridization with a 23S-5S B. subtilis ribosomal sequence probe verified that they are indistinguishable from laboratory strains of Bacillus cereus.

Effectiveness of an Integrated Pest Management Intervention in Controlling Cockroaches, Mice, and Allergens in New York City Public Housing

Science.gov (United States)

Kass, Daniel; McKelvey, Wendy; Carlton, Elizabeth; Hernandez, Marta; Chew, Ginger; Nagle, Sean; Garfinkel, Robin; Clarke, Brian; Tiven, Julius; Espino, Christian; Evans, David

2009-01-01

Background Cockroaches and mice, which are common in urban homes, are sources of allergens capable of triggering asthma symptoms. Traditional pest control involves the use of scheduled applications of pesticides by professionals as well as pesticide use by residents. In contrast, integrated pest management (IPM) involves sanitation, building maintenance, and limited use of least toxic pesticides. Objectives We implemented and evaluated IPM compared with traditional practice for its impact on pests, allergens, pesticide use, and resident satisfaction in a large urban public housing authority. Methods We assigned IPM or control status to 13 buildings in five housing developments, and evaluated conditions at baseline, 3 months, and 6 months in 280 apartments in Brooklyn and Manhattan, in New York City (New York). We measured cockroach and mouse populations, collected cockroach and mouse urinary protein allergens in dust, and interviewed residents. All statistical models controlled for baseline levels of pests or allergens. Results Compared with controls, apartments receiving IPM had significantly lower counts of cockroaches at 3 months and greater success in reducing or sustaining low counts of cockroaches at both 3 and 6 months. IPM was associated with lower cockroach allergen levels in kitchens at 3 months and in beds and kitchens at 6 months. Pesticide use was reduced in IPM relative to control apartments. Residents of IPM apartments also rated building services more positively. Conclusions In contrast to previous IPM studies, which involved extensive cleaning, repeat visits, and often extensive resident education, we found that an easily replicable single IPM visit was more effective than the regular application of pesticides alone in managing pests and their consequences. PMID:19672400

Insecticidal Properties of Essential Oils and Some of Their Constituents on the Turkestan Cockroach (Blattodea: Blattidae).

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Gaire, Sudip; O'Connell, Mary; Holguin, Francisco O; Amatya, Anup; Bundy, Scott; Romero, Alvaro

2017-04-01

The Turkestan cockroach, Blatta lateralis (Walker), has become the most important peridomestic species in urban areas of the Southwestern United States. The aim of this study was to evaluate the use of botanical compounds to control this urban pest. We tested the acute toxicity and repellency of six botanical constituents and three essential oils on Turkestan cockroach nymphs. Chemical composition of the essential oils was also determined. Topical and fumigant assays with nymphs showed that thymol was the most toxic essential oil constituent, with a LD50 of 0.34 mg/nymph and a LC50 of 27.6 mg/liter air, respectively. Contact toxicity was also observed in assays with trans-Cinnamaldehyde, eugenol, geraniol, methyl eugenol, and p-Cymene. Methyl eugenol and geraniol had limited fumigant toxicity. The essential oils from red thyme, clove bud, and Java citronella exhibited toxicity against nymphs. Cockroaches avoided fresh dry residues of thymol and essential oils. Chemical analysis of the essential oils confirmed high contents of effective essential oil constituents. Our results demonstrated that essential oils and some of their constituents have potential as eco-friendly insecticides for the management of Turkestan cockroaches. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

IgE-Binding Epitope Mapping and Tissue Localization of the Major American Cockroach Allergen Per a 2.

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Lee, Mey Fann; Chang, Chia Wei; Song, Pei Pong; Hwang, Guang Yuh; Lin, Shyh Jye; Chen, Yi Hsing

2015-07-01

Cockroaches are the second leading allergen in Taiwan. Sensitization to Per a 2, the major American cockroach allergen, correlates with clinical severity among patients with airway allergy, but there is limited information on IgE epitopes and tissue localization of Per a 2. This study aimed to identify Per a 2 linear IgE-binding epitopes and its distribution in the body of a cockroach. The cDNA of Per a 2 was used as a template and combined with oligonucleotide primers specific to the target areas with appropriate restriction enzyme sites. Eleven overlapping fragments of Per a 2 covering the whole allergen molecule, except 20 residues of signal peptide, were generated by PCR. Mature Per a 2 and overlapping deletion mutants were affinity-purified and assayed for IgE reactivity by immunoblotting. Three synthetic peptides comprising the B cell epitopes were evaluated by direct binding ELISA. Rabbit anti-Per a 2 antibody was used for immunohistochemistry. Human linear IgE-binding epitopes of Per a 2 were located at the amino acid sequences 57-86, 200-211, and 299-309. There was positive IgE binding to 10 tested Per a 2-allergic sera in 3 synthetic peptides, but none in the controls. Immunostaining revealed that Per a 2 was localized partly in the mouth and midgut of the cockroach, with the most intense staining observed in the hindgut, suggesting that the Per a 2 allergen might be excreted through the feces. Information on the IgE-binding epitope of Per a 2 may be used for designing more specific diagnostic and therapeutic approaches to cockroach allergy.

Alveolar Macrophages Play a Key Role in Cockroach-Induced Allergic Inflammation via TNF-α Pathway

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Kim, Joo Young; Sohn, Jung Ho; Choi, Je-Min; Lee, Jae-Hyun; Hong, Chein-Soo; Lee, Joo-Shil; Park, Jung-Won

2012-01-01

The activity of the serine protease in the German cockroach allergen is important to the development of allergic disease. The protease-activated receptor (PAR)-2, which is expressed in numerous cell types in lung tissue, is known to mediate the cellular events caused by inhaled serine protease. Alveolar macrophages express PAR-2 and produce considerable amounts of tumor necrosis factor (TNF)-α. We determined whether the serine protease in German cockroach extract (GCE) enhances TNF-α production by alveolar macrophages through the PAR-2 pathway and whether the TNF-α production affects GCE-induced pulmonary inflammation. Effects of GCE on alveolar macrophages and TNF-α production were evaluated using in vitro MH-S and RAW264.6 cells and in vivo GCE-induced asthma models of BALB/c mice. GCE contained a large amount of serine protease. In the MH-S and RAW264.7 cells, GCE activated PAR-2 and thereby produced TNF-α. In the GCE-induced asthma model, intranasal administration of GCE increased airway hyperresponsiveness (AHR), inflammatory cell infiltration, productions of serum immunoglobulin E, interleukin (IL)-5, IL-13 and TNF-α production in alveolar macrophages. Blockade of serine proteases prevented the development of GCE induced allergic pathologies. TNF-α blockade also prevented the development of such asthma-like lesions. Depletion of alveolar macrophages reduced AHR and intracellular TNF-α level in pulmonary cell populations in the GCE-induced asthma model. These results suggest that serine protease from GCE affects asthma through an alveolar macrophage and TNF-α dependent manner, reflecting the close relation of innate and adaptive immune response in allergic asthma model. PMID:23094102

The Optic Lobes Regulate Circadian Rhythms of Olfactory Learning and Memory in the Cockroach.

Science.gov (United States)

Lubinski, Alexander J; Page, Terry L

2016-04-01

The cockroach, Leucophaea maderae, can be trained in an associative olfactory memory task by either classical or operant conditioning. When trained by classical conditioning, memory formation is regulated by a circadian clock, but once the memory is formed, it can be recalled at any circadian time. In contrast, when trained via operant conditioning, animals can learn the task at any circadian phase, but the ability to recall the long-term memory is tied to the phase of training. The optic lobes of the cockroach contain a circadian clock that drives circadian rhythms of locomotor activity, mating behavior, sensitivity of the compound eye to light, and the sensitivity of olfactory receptors in the antennae. To evaluate the role of the optic lobes in regulating learning and memory processes, the authors examined the effects of surgical ablation of the optic lobes on memory formation in classical conditioning and memory recall following operant conditioning. The effect of optic lobe ablation was to "rescue" the deficit in memory acquisition at a time the animals normally cannot learn and "rescue" the animal's ability to recall a memory formed by operant conditioning at a phase where memory was not normally expressed. The results suggested that the optic lobe pacemaker regulates these processes through inhibition at "inappropriate" times of day. As a pharmacological test of this hypothesis, the authors showed that injections of fipronil, an antagonist of GABA and glutamate-activated chloride channels, had the same effects as optic lobe ablation on memory formation and recall. The data suggest that the optic lobes contain the circadian clock(s) that regulate learning and memory processes via inhibition of neural processes in the brain. © 2015 The Author(s).

COCKROACHES, PESTICIDE USE, AND CHILDREN'S PULMONARY FUNCTION IN AN ARID COMMUNITY

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Cockroaches, pesticide use, and children's pulmonary function in an arid communityErik Svendsen1, Mary Ross1, Melissa Gonzales2, Debra Walsh1, Scott Rhoney1, Gina Terrill1, Lucas Neas11US EPA, Chapel Hill, NC; 2University of New MexicoThe El Paso Children's He...

Toxicity of entomopathogenic fungi, Beauveria bassiana and Lecanicillium muscarium against a field-collected strain of the German cockroach Blattella germanica (L.) (Dictyoptera: Blattellidae).

Science.gov (United States)

Davari, B; Limoee, M; Khodavaisy, S; Zamini, G; Izadi, S

2015-09-01

The German cockroach, Blattella germanica (L.) has been recognized as a serious health problem throughout the world. Control failures due to insecticide resistance and chemical contamination of environment have led some researchers focus on the other alternative strategy controls. Microbial insecticides such as those containing entomo pathogenic fungi could be of high significance. Lecanicillium muscarium and Beauveria bassiana grow naturally in soils throughout the world and act as a parasite on various arthropod species, causing white muscardine disease. Thus, these two species could be considered as entomopathogenic fungi. The current study conducted to evaluate the toxicity of Beauveria bassiana and Lecanicillium muscarium against German cockroach, Blattella germanica. Conidial formulations of L. muscarium (PTCC 5184) and B. bassiana (PTCC5197) were prepared in aqueous suspensions with Tween 20. Bioassays were performed using two methods including submersion of cockroaches in conidial suspension and baiting. Data were analyzed by Probit program and LC50 and LC90 were estimated. The obtained results indicated that both fungi species were toxic against German cockroach however; Beauveria bassiana was significantly 4.8 fold more toxic than L. muscarium against German cockroach using submersion method.

Effects of neck and circumoesophageal connective lesions on posture and locomotion in the cockroach.

Science.gov (United States)

Ridgel, Angela L; Ritzmann, Roy E

2005-06-01

Few studies in arthropods have documented to what extent local control centers in the thorax can support locomotion in absence of inputs from head ganglia. Posture, walking, and leg motor activity was examined in cockroaches with lesions of neck or circumoesophageal connectives. Early in recovery, cockroaches with neck lesions had hyper-extended postures and did not walk. After recovery, posture was less hyper-extended and animals initiated slow leg movements for multiple cycles. Neck lesioned individuals showed an increase in walking after injection of either octopamine or pilocarpine. The phase of leg movement between segments was reduced in neck lesioned cockroaches from that seen in intact animals, while phases in the same segment remained constant. Neither octopamine nor pilocarpine initiated changes in coordination between segments in neck lesioned individuals. Animals with lesions of the circumoesophageal connectives had postures similar to intact individuals but walked in a tripod gait for extended periods of time. Changes in activity of slow tibial extensor and coxal depressor motor neurons and concomitant changes in leg joint angles were present after the lesions. This suggests that thoracic circuits are sufficient to produce leg movements but coordinated walking with normal motor patterns requires descending input from head ganglia.

Population ecology and movement of the American cockroach (Dictyoptera: Blattidae) in sewers.

Science.gov (United States)

Tee, Hui-Siang; Saad, Ahmad Ramli; Lee, Chow-Yang

2011-07-01

The population size, age-class structure, and movement of the American cockroach, Periplaneta americana (L.) (Dictyoptera: Blattidae), were studied in three sewers in Penang, Malaysia, from September 2008 to October 2009. Eighteen to 20 glass-jar traps (two per manhole) were deployed for a 24-h period during each sampling occasion at each sewer. Adults and nymphs were active throughout the study period, with an average monthly trap catch of 57-97 adults and 79-99 nymphs. The mean proportions of adults and nymphs at the three sewers ranged from 0.47 to 0.57. Of the 2177 male and 2717 female cockroaches marked and released over the three sewers, recapture rates were 29.4-45.8 and 30.8-47.0%, respectively. The proportion of marked males and females did not differ significantly from the proportion of recaptured marked males and females. However, the mean number of times a marked female was recaptured was significantly greater than that of males. Of the 783 males and 1,030 females that were marked and recaptured, 19.4 and 24.7%, respectively, had moved between manholes, and significantly more females than males moved between manholes. Of the 406 recaptured marked adults that moved between manholes, 90.4% moved a distance of 2-20 m from their initial release site; one male moved 192 m, the longest distance recorded. Trap catch on each sampling occasion was positively correlated with daily mean temperature. The number of cockroach movements between manholes also was correlated with the mean daily minimum temperature.

The Core Gut Microbiome of the American Cockroach, Periplaneta americana, Is Stable and Resilient to Dietary Shifts.

Science.gov (United States)

Tinker, Kara A; Ottesen, Elizabeth A

2016-11-15

The omnivorous cockroach Periplaneta americana hosts a diverse hindgut microbiota encompassing hundreds of microbial species. In this study, we used 16S rRNA gene sequencing to examine the effect of diet on the composition of the P. americana hindgut microbial community. Results show that the hindgut microbiota of P. americana exhibit a highly stable core microbial community with low variance in compositions between individuals and minimal community change in response to dietary shifts. This core hindgut microbiome is shared between laboratory-hosted and wild-caught individuals, although wild-caught specimens exhibited a higher diversity of low-abundance microbes that were lost following extended cultivation under laboratory conditions. This taxonomic stability strongly contrasts with observations of the gut microbiota of mammals, which have been shown to be highly responsive to dietary change. A comparison of P. americana hindgut samples with human fecal samples indicated that the cockroach hindgut community exhibited higher alpha diversity but a substantially lower beta diversity than the human gut microbiome. This suggests that cockroaches have evolved unique mechanisms for establishing and maintaining a diverse and stable core microbiome. The gut microbiome plays an important role in the overall health of its host. A healthy gut microbiota typically assists with defense against pathogens and the digestion and absorption of nutrients from food, while dysbiosis of the gut microbiota has been associated with reduced health. In this study, we examined the composition and stability of the gut microbiota from the omnivorous cockroach Periplaneta americana. We found that P. americana hosts a diverse core gut microbiome that remains stable after drastic long-term changes in diet. While other insects, notably ant and bee species, have evolved mechanisms for maintaining a stable association with specific gut microbiota, these insects typically host low-diversity gut

Tomaculocystis corpulenta n. gen., n. sp. (Apicomplexa: Eugregarinorida) parasitizing the little yellow cockroach, Cariblatta lutea (Blattodea: Ectobiidae), in Alabama and Florida with recognition of Tomaculocystis cylindrosa n. comb. and Tomaculocystis mukundai n. comb. parasitizing ectobiid cockroaches in India.

Science.gov (United States)

Clopton, Richard E

2015-02-01

Tomaculocystis corpulenta n. gen., n. sp. (Apicomplexa: Eugregarinorida: Septatorina: Gregarinidae) is described from populations of the little yellow cockroach, Cariblatta lutea (Blattodea: Ectobiidae), established in laboratory culture from samples collected in Alabama and Florida. Tomaculocystis n. gen. are differentiated from other members of Gregarina by a markedly elliptoid gametocyst inside a persistent, lomentiform hyaline epicyst; developmental organization and growth of the spore tubes from gametocyst surface tumidi; and dehiscence by extrusion of non-chain forming oocysts through spore tubes that barely extend beyond the epicyst wall. Gregarina cylindrosa, Gregarina discocephala, and Gregarina mukundai are recognized as members of Tomaculocystis, and G. cylindrosa is recognized as the senior synonym of G. discocephala. Thus, Tomaculocystis cylindrosa n. comb. and Tomaculocystis mukundai n. comb. are formed. Species of Tomaculocystis are distinguished based on gamont deutomerite and oocyst shape and size. The oocysts of T. corpulenta are broadly dolioform, lack 4 polar knobs, and possess distinct, unique polar plates. Oocysts of all other known species in the genus are more oblong in shape, possess 4 polar knobs, and lack the distinct polar plates observed in the oocysts of T. corpulenta. Host utilization and geographic distribution among gregarine genera parasitizing the cockroach family Ectobiidae reveal a pattern of host-parasite specificity linking gregarine genera with ectobiidid subfamilies. Overall patterns suggest a hypothesis of European endemicy for Gamocystis, but hypotheses for the origin and radiation of Tomaculocystis or species of Gregarina infecting cockroaches are confounded by the cosmopolitan spread of pest cockroach species among humans.

Distribution of Thelastomatoid Nematodes (Nematoda: Oxyurida) in Endemic and Introduced Cockroaches on the Galápagos Island Archipelago, Ecuador.

Science.gov (United States)

Sinnott, Devinn; Carreno, Ramon A; Herrera, Henri

2015-08-01

The thelastomatoid pinworm fauna (Nematoda: Oxyurida: Thelastomatoidea) was surveyed in 3 endemic species and 6 introduced species of cockroach hosts (Insecta: Blattaria) in the Galápagos Islands, Ecuador. A total of 658 host specimens were examined from preserved collections that had been collected between 1966 and 2003 from 7 islands in the archipelago. Eight species of pinworms were identified from these cockroach hosts, including the dominant species Cephalobellus ovumglutinosus and a Severianoia sp. as well as Leidynema appendiculata, Hammerschmidtiella diesingi, an unidentified Cephalobellus species resembling Cephalobellus magalhaesi, an unidentified Protrellus species closely resembling Protrellus shamimi, and an undescribed Blattophila sp. Five new host records are identified for C. ovumglutinosus including the endemic Galápagos cockroaches Chorisoneura carpenteri, Ischnoptera snodgrassii, and Ischnoptera santacruzensis. These endemics were also infected with an undescribed Blatticola sp. Other species recorded resemble known pinworms from other hosts around the world. Prevalence between islands and between host species was variable, but total prevalence for individual pinworm species was consistently low (<10%). A single host specimen examined was infected with more than 1 pinworm species; otherwise only a single species was observed in each infected host. At least 1 introduced pinworm species carried to the islands via invasive cockroach hosts was present in endemic host species, but several globally widespread introduced pinworm species were absent from endemic cockroaches. Santa Cruz was inhabited by the greatest number of pinworm species, likely due to a higher rate of invasive host introduction. This survey, the first from this region, showed that the distribution and transmission of pinworms in the Galápagos Islands is complex and may provide future models of invertebrate dispersal and speciation in an ecosystem already rich with examples of

Leg Regrowth in Blaberus discoidalis (Discoid Cockroach) following Limb Autotomy versus Limb Severance and Relevance to Neurophysiology Experiments

Science.gov (United States)

Marzullo, Timothy C.

2016-01-01

Background Many insects can regenerate limbs, but less is known about the regrowth process with regard to limb injury type. As part of our neurophysiology education experiments involving the removal of a cockroach leg, 1) the ability of Blaberus discoidalis cockroaches to regenerate a metathoracic leg was examined following autotomy at the femur/trochanter joint versus severance via a transverse coxa-cut, and 2) the neurophysiology of the detached legs with regard to leg removal type was studied by measuring spike firing rate and microstimulation movement thresholds. Leg Regrowth Results First appearance of leg regrowth was after 5 weeks in the autotomy group and 12 weeks in the coxa-cut group. Moreover, regenerated legs in the autotomy group were 72% of full size on first appearance, significantly larger (pbarbs, and a 10% higher electrical microstimulation threshold for movement. Summary It is recommended that neurophysiology experiments on cockroach legs remove the limb at autotomy joints instead of coxa cuts, as the leg regenerates significantly faster when autotomized and does not detract from the neurophysiology educational content. PMID:26824931

Pest Prevalence and Evaluation of Community-Wide Integrated Pest Management for Reducing Cockroach Infestations and Indoor Insecticide Residues.

Science.gov (United States)

Zha, Chen; Wang, Changlu; Buckley, Brian; Yang, Ill; Wang, Desen; Eiden, Amanda L; Cooper, Richard

2018-04-02

Pest infestations in residential buildings are common, but community-wide pest survey data are lacking. Frequent insecticide applications for controlling indoor pests leave insecticide residues and pose potential health risks to residents. In this study, a community-wide pest survey was carried out in a housing complex consisting of 258 units in 40 buildings in New Brunswick, New Jersey. It was immediately followed by implementation of an integrated pest management (IPM) program in all the cockroach-infested apartments and two bed bug apartments with the goal of eliminating pest infestations, reducing pyrethroid residues, and increasing resident satisfaction with pest control services. The IPM-treated apartments were revisited and treated biweekly or monthly for 7 mo. Initial inspection found the top three pests and their infestation rates to be as follows: German cockroaches (Blattella germanica L. [Blattodea: Blattellidae]), 28%; rodents, 11%; and bed bugs (Cimex lectularius L. [Hemiptera: Cimicidae]), 8%. Floor wipe samples were collected in the kitchens and bedrooms of 20 apartments for pyrethroid residue analysis before the IPM implementation; 17 of the 20 apartments were resampled again at 7 mo. The IPM program reduced cockroach counts per apartment by 88% at 7 wk after initial treatment. At 7 mo, 85% of the cockroach infestations found in the initial survey were eliminated. The average number of pyrethroids detected decreased significantly from 6 ± 1 (mean ± SEM) and 5 ± 1 to 2 ± 1 and 3 ± 1 in the kitchens and bedrooms, respectively. The average concentrations of targeted pyrethroids residue also decreased significantly in the kitchens and bedrooms.

Some Guides to Discovery About Elm Trees, Owls, Cockroaches, Earthworms, Cement and Concrete.

Science.gov (United States)

Busch, Phyllis S.

The introduction emphasizes the need for environmental and conservation education, and advocates an inquiry approach. Outdoor resources available to every school are listed. Detailed suggestions are made for investigating cement and concrete, cockroaches, earthworms, elm trees, and owls. In each case general background information and a list of…

Comparative study of specific IgE for cockroach between asthma and allergic rhinitis patients

International Nuclear Information System (INIS)

Guo Yinshi; Xu Yiping; Zhu Lijun; Wang Limin; Cao Lingxian; Yao Suhang

2005-01-01

To compare the degrees of allergic reaction and the cross-reactive allergens for three strains of cockroach (Periplanceta fuliginosa , Periplaneta americana and Blattella germanica) between patients with asthma and allergic rhinitis, the specific IgE(sIgE) in asthma and allergic rhinitis for these three strains of cockroach were determined with ELISA. The results showed that the sIgE positive rates for Periplaneta americana, Periplaneta fuliginosa and Blattella germanica in patients with asthma were 23.5%, 16.0% and 14.8%, respectively. The reactive coincidence rate between Periplaneta americana and Periplaneta fuliginoas was 74.0%, between Periplaneta americana and Blattella germanica was 73.5%, and between Periplaneta fuliginosa and Blattella germanica was 85.0% in asthma patients. The IgE positive rates for Periplaneta americana, Periplaneta fuliginosa and Blattella gerraanica in allergic rhinitis patients were 24.8%, 17.6% and 15.8%, respectively. The reactive coincidence rate between Periplaneta americana and Periplaneta fuliginosa was 73.9%, between Periplaneta americana and Blattella germanica was 75.2%, and between Periplaneta fuliginosa and Blattella germanica was 86.1% in allergic rhinitis patients. There was no significant difference between asthma and allergic rhinitis patients although the sIgE positive rates of allergic rhinitis patients were higher than those of asthma patients for these three strains of cock- roach. All these results indicated that the degrees of allergic reaction are similar between asthma and allergic rhinitis patients and there are some cross-reactive allergic components among these three strains of cockroach. (authors)

[Asymmetry of antennal grooming in the cockroach (Periplaneta americana)].

Science.gov (United States)

2014-07-01

The present study was conducted to determine the key features of antennal grooming of male American cockroaches in neutral circumstances. It was shown for the first time that the right antenna was cleaned significantly more often than the left one, which indicates the presence of functional asymmetry of antennal grooming in this insect species. At the same time, no statistically significant asymmetry was found for grooming of antennal bases and legs. Morphological asymmetries of antennae and legs and/or brain lateralization are the plausible sources of observed behavioral asymmetry in antennal grooming.

Analysis of Cockroach Fauna and Frequency in Human Residential Habitats of North of Isfahan, Iran

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Dehghani R.1 PhD,

2016-08-01

Full Text Available Aims Considering the medical significance of cockroaches as insect vectors of food toxicities, and triggering allergy in respiratory system and skin, this survey was conducted to study the frequency of infestation and their effective factors in Shahin Shahr, Iran. Materials & Methods This cross-sectional descriptive study was carried out in 2010 in Shahin Shahr, Isfahan, Iran. Data gathering instrument was a researcher-made questionnaire regarding to the research aims. Data were analyzed by SPSS 11.5 software using Chi square and Fisher exact tests. Findings 675 of 1000 studied houses (67.5% were infested by all life stages of the cockroaches and 32.5% had no infestation. 46% of infested houses had few, 30% had medium and 24% had high infestation. the bathrooms and toilets were recognized as the most infested places (41%. There were significant relationships between infestation of houses and the age of building (p<0.001, the type of building (p=0.009 and the education level of the family (p<0.001. Significant difference was found between houses equipped their doors and windows by tulles and without tulles (p=0.03. Most infection was found in houses sheltering 5 and more people (72.3%. Significant correlation was found between the infection and the number of family members (p=0.0012. Conclusion Infestation rate of cockroaches in Shahin Shahr houses is high and is mostly of P. americana species.

Endogenous rhythm and pattern-generating circuit interactions in cockroach motor centres

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Izhak David

2016-09-01

Full Text Available Cockroaches are rapid and stable runners whose gaits emerge from the intricate, and not fully resolved, interplay between endogenous oscillatory pattern-generating networks and sensory feedback that shapes their rhythmic output. Here we studied the endogenous motor output of a brainless, deafferented preparation. We monitored the pilocarpine-induced rhythmic activity of levator and depressor motor neurons in the mesothoracic and metathoracic segments in order to reveal the oscillatory networks’ architecture and interactions. Data analyses included phase relations, latencies between and overlaps of rhythmic bursts, spike frequencies, and the dependence of these parameters on cycle frequency. We found that, overall, ipsilateral connections are stronger than contralateral ones. Our findings revealed asymmetries in connectivity among the different ganglia, in which meta-to-mesothoracic ascending coupling is stronger than meso-to-metathoracic descending coupling. Within-ganglion coupling between the metathoracic hemiganglia is stronger than that in the mesothoracic ganglion. We also report differences in the role and mode of operation of homologue network units (manifested by levator and depressor nerve activity. Many observed characteristics are similar to those exhibited by intact animals, suggesting a dominant role for feedforward control in cockroach locomotion. Based on these data we posit a connectivity scheme among components of the locomotion pattern generating system.

Cuticle Fatty Acid Composition and Differential Susceptibility of Three Species of Cockroaches to the Entomopathogenic Fungi Metarhizium anisopliae (Ascomycota, Hypocreales).

Science.gov (United States)

Gutierrez, Alejandra C; Gołębiowski, Marek; Pennisi, Mariana; Peterson, Graciela; García, Juan J; Manfrino, Romina G; López Lastra, Claudia C

2015-04-01

Differences in free fatty acids (FFAs) chemical composition of insects may be responsible for susceptibility or resistance to fungal infection. Determination of FFAs found in cuticular lipids can effectively contribute to the knowledge concerning insect defense mechanisms. In this study, we have evaluated the susceptibility of three species of cockroaches to the entomopathogenic fungi Metarhizium anisopliae (Metschnikoff) Sorokin by topical application. Mortality due to M. anisopliae was highly significant on adults and nymphs of Blattella germanica L. (Blattodea: Blattellidae). However, mortality was faster in adults than in nymphs. Adults of Blatta orientalis L. (Blattodea: Blattidae) were not susceptible to the fungus, and nymphs of Blaptica dubia Serville (Blattodea: Blaberidae) were more susceptible to the fungus than adults. The composition of cuticular FFAs in the three species of cockroaches was also studied. The analysis indicated that all of the fatty acids were mostly straight-chain, long-chain, saturated or unsaturated. Cuticular lipids of three species of cockroaches contained 19 FFAs, ranging from C14:0 to C24:0. The predominant fatty acids found in the three studied species of cockroaches were oleic, linoleic, palmitic, and stearic acid. Only in adults of Bl. orientalis, myristoleic acid, γ-linolenic acid, arachidic acid, dihomolinoleic acid, and behenic acid were identified. Lignoceric acid was detected only in nymphs of Bl. orientalis. Heneicosylic acid and docosahexaenoic acid were identified in adults of Ba. dubia. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Aerobic Bacterial Community of American Cockroach Periplaneta americana,a Step toward Finding Suitable Paratransgenesis Candidates.

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Akbari, Sanaz; Oshaghi, Mohammad Ali; Hashemi-Aghdam, Saedeh Sadat; Hajikhani, Sara; Oshaghi, Ghazaleh; Shirazi, Mohammad Hasan

2015-06-01

Cockroaches mechanically spread pathogenic agents, however, little is known about their gut microbiota. Identification of midgut microbial community helps targeting novel biological control strategies such as paratransgenesis. Here the bacterial microbiota of Periplaneta americana midgut, were identified and evaluated for finding proper paratransgenesis candidate. Midgut of specimens were dissected and cultivated in different media. The bacterial isolates were then identified using the phenotypic and 16S-rRNA sequencing methods. The analytical profile index (API) kit showed presence of 11 bacterial species including: Escherichia coli, Shigella flexineri, Citrobacter freundii, E. vulneris, Enterobacter cloacae, Yersinia pseudotuberculosis, Y. intermedia, Leclericia adecarboxylata, Klebsiella oxytoca, K. planticola, and Rahnella aquatilis in the cockroach midguts. The first three species are potentially symbiotic whereas others are transient. The conventional plating method revealed presence of only four isolates of Salmonella, E. coli, and Proteus which in three cases mismatched with API and 16S-rRNA genotyping. The API correctly identified the four isolates as Shigella flexneri, Citrobacter freundii, and E. coli (n= 2). 16S-rRNA sequence analysis confirmed the API results; however the C. freundii sequence was identical with C. murliniae indicating lack of genetic variation in the gene between these two closely related species. A low number of potentially symbiotic bacteria were found in the American cockroach midguts. Among them Enterobacter cloacae is a potential candidate for paratransgenesis approach whereas other bacteria are pathogens and are not useful for the approach. Data analysis showed that identification levels increase from the conventional to API and to genotyping respectively.

Aerobic Bacterial Community of American Cockroach Periplaneta americana,a Step toward Finding Suitable Paratransgenesis Candidates

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Sanaz Akbari

2015-10-01

Full Text Available Background: Cockroaches mechanically spread pathogenic agents, however, little is known about their gut microbiota. Identification of midgut microbial community helps targeting novel biological control strategies such as paratransgenesis. Here the bacterial microbiota of Periplaneta americana midgut, were identified and evaluated for finding proper paratransgenesis candidate.Methods: Midgut of specimens were dissected and cultivated in different media. The bacterial isolates were then identified using the phenotypic and 16S-rRNA sequencing methods.Results: The analytical profile index (API kit showed presence of 11 bacterial species including: Escherichia coli, Shigella flexineri, Citrobacter freundii, E. vulneris, Enterobacter cloacae, Yersinia pseudotuberculosis, Y.intermedia, Leclericia adecarboxylata, Klebsiella oxytoca, K. planticola, and Rahnella aquatilis in the cockroach midguts. The first three species are potentially symbiotic whereas others are transient. The conventional platingmethod revealed presence of only four isolates of Salmonella, E. coli, and Proteus which in three cases mismatched with API and 16S-rRNA genotyping. The API correctly identified the four isolates as Shigella flexneri, Citrobacter freundii, and E. coli (n= 2. 16S-rRNA sequence analysis confirmed the API results; however the C. freundii sequencewas identical with C. murliniae indicating lack of genetic variation in the gene between these two closely related species.Conclusion: A low number of potentially symbiotic bacteria were found in the American cockroach midguts. Among them Enterobacter cloacae is a potential candidate for paratransgenesis approach whereas other bacteria are pathogens and are not useful for the approach. Data analysis showed that identification levels increase from the conventional to API and to genotyping respectively.

The orange spotted cockroach (Blaptica dubia, Serville 1839) is a permissive experimental host for Francisella tularensis

Science.gov (United States)

Eklund, Bridget E.; Mahdi, Osama; Huntley, Jason F.; Collins, Elliot; Martin, Caleb; Horzempa, Joseph; Fisher, Nathan A.

2018-01-01

Francisella tularensis is a zoonotic bacterial pathogen that causes severe disease in a wide range of host animals, including humans. Well-developed murine models of F. tularensis pathogenesis are available, but they do not meet the needs of all investigators. However, researchers are increasingly turning to insect host systems as a cost-effective alternative that allows greater increased experimental throughput without the regulatory requirements associated with the use of mammals in biomedical research. Unfortunately, the utility of previously-described insect hosts is limited because of temperature restriction, short lifespans, and concerns about the immunological status of insects mass-produced for other purposes. Here, we present a novel host species, the orange spotted (OS) cockroach (Blaptica dubia), that overcomes these limitations and is readily infected by F. tularensis. Intrahemocoel inoculation was accomplished using standard laboratory equipment and lethality was directly proportional to the number of bacteria injected. Progression of infection differed in insects housed at low and high temperatures and F. tularensis mutants lacking key virulence components were attenuated in OS cockroaches. Finally, antibiotics were delivered to infected OS cockroaches by systemic injection and controlled feeding; in the latter case, protection correlated with oral bioavailability in mammals. Collectively, these results demonstrate that this new host system provides investigators with a new tool capable of interrogating F. tularensis virulence and immune evasion in situations where mammalian models are not available or appropriate, such as undirected screens of large mutant libraries. PMID:29578544

Caffeine-supplemented diet modulates oxidative stress markers and improves locomotor behavior in the lobster cockroach Nauphoeta cinerea.

Science.gov (United States)

da Silva, Cícera Simoni; de Cássia Gonçalves de Lima, Rita; Elekofehinti, Olusola Olalekan; Ogunbolude, Yetunde; Duarte, Antonia Eliene; Rocha, João Batista Teixeira; Alencar de Menezes, Irwin Rose; Barros, Luiz Marivando; Tsopmo, Appolinaire; Lukong, Kiven Erique; Kamdem, Jean Paul

2018-02-25

The effects of caffeine supplementation is well documented in conventional animal models, however, in the lobster cockroaches Nauphoeta cinerea, they have not been reported. Thus, the aim of this study was to investigate the locomotor behavior and biochemical endpoints in the head of the nymphs of N. cinerea following 60 days exposure to food supplemented with 0, 0.5, 1.0, 2.5, 5.0 and 10.0 mg of caffeine/g of diet. The analysis of the locomotor behavior using the video-tracking software, Any-maze, for 12 min revealed that caffeine supplementation caused significant behavioral improvement. There was increase in distance travelled, velocity, frequency of rotation and turn angle (stereotypical behavior such as circling movements), and this was supported by the representative track plots of the path travelled by cockroaches in the open-field arena. In addition, caffeine supplementation markedly increased total thiol and non-protein thiol glutathione (GSH) levels in the heads of cockroaches, and this was in parallel with significant reduction of lipid peroxidation and free Fe(II) content. Taking together, our results indicate that long-term caffeine supplementation may exert preventive effects against oxidative stress and support the use of N. cinerea as an efficient alternative model to assess the efficacy of food molecules. Copyright © 2018 Elsevier B.V. All rights reserved.

Receptor for advanced glycation end products and its ligand high-mobility group box-1 mediate allergic airway sensitization and airway inflammation.

Science.gov (United States)

Ullah, Md Ashik; Loh, Zhixuan; Gan, Wan Jun; Zhang, Vivian; Yang, Huan; Li, Jian Hua; Yamamoto, Yasuhiko; Schmidt, Ann Marie; Armour, Carol L; Hughes, J Margaret; Phipps, Simon; Sukkar, Maria B

2014-08-01

The receptor for advanced glycation end products (RAGE) shares common ligands and signaling pathways with TLR4, a key mediator of house dust mite (Dermatophagoides pteronyssinus) (HDM) sensitization. We hypothesized that RAGE and its ligand high-mobility group box-1 (HMGB1) cooperate with TLR4 to mediate HDM sensitization. To determine the requirement for HMGB1 and RAGE, and their relationship with TLR4, in airway sensitization. TLR4(-/-), RAGE(-/-), and RAGE-TLR4(-/-) mice were intranasally exposed to HDM or cockroach (Blatella germanica) extracts, and features of allergic inflammation were measured during the sensitization or challenge phase. Anti-HMGB1 antibody and the IL-1 receptor antagonist Anakinra were used to inhibit HMGB1 and the IL-1 receptor, respectively. The magnitude of allergic airway inflammation in response to either HDM or cockroach sensitization and/or challenge was significantly reduced in the absence of RAGE but not further diminished in the absence of both RAGE and TLR4. HDM sensitization induced the release of HMGB1 from the airway epithelium in a biphasic manner, which corresponded to the sequential activation of TLR4 then RAGE. Release of HMGB1 in response to cockroach sensitization also was RAGE dependent. Significantly, HMGB1 release occurred downstream of TLR4-induced IL-1α, and upstream of IL-25 and IL-33 production. Adoptive transfer of HDM-pulsed RAGE(+/+)dendritic cells to RAGE(-/-) mice recapitulated the allergic responses after HDM challenge. Immunoneutralization of HMGB1 attenuated HDM-induced allergic airway inflammation. The HMGB1-RAGE axis mediates allergic airway sensitization and airway inflammation. Activation of this axis in response to different allergens acts to amplify the allergic inflammatory response, which exposes it as an attractive target for therapeutic intervention. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Modeling population dynamics of two cockroach species: Effects of the circadian clock, interspecific competition and pest control

Czech Academy of Sciences Publication Activity Database

Wu, H. H.; Lee, H. J.; Horng, S. B.; Berec, Luděk

2007-01-01

Roč. 249, - (2007), s. 473-486 ISSN 0022-5193 Institutional research plan: CEZ:AV0Z50070508 Keywords : German cockroach * Blattella germanica * Blatella bisignata Subject RIV: EH - Ecology, Behaviour Impact factor: 2.323, year: 2007

Evolutionary convergence and nitrogen metabolism in Blattabacterium strain Bge, primary endosymbiont of the cockroach Blattella germanica.

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Maria J López-Sánchez

2009-11-01

Full Text Available Bacterial endosymbionts of insects play a central role in upgrading the diet of their hosts. In certain cases, such as aphids and tsetse flies, endosymbionts complement the metabolic capacity of hosts living on nutrient-deficient diets, while the bacteria harbored by omnivorous carpenter ants are involved in nitrogen recycling. In this study, we describe the genome sequence and inferred metabolism of Blattabacterium strain Bge, the primary Flavobacteria endosymbiont of the omnivorous German cockroach Blattella germanica. Through comparative genomics with other insect endosymbionts and free-living Flavobacteria we reveal that Blattabacterium strain Bge shares the same distribution of functional gene categories only with Blochmannia strains, the primary Gamma-Proteobacteria endosymbiont of carpenter ants. This is a remarkable example of evolutionary convergence during the symbiotic process, involving very distant phylogenetic bacterial taxa within hosts feeding on similar diets. Despite this similarity, different nitrogen economy strategies have emerged in each case. Both bacterial endosymbionts code for urease but display different metabolic functions: Blochmannia strains produce ammonia from dietary urea and then use it as a source of nitrogen, whereas Blattabacterium strain Bge codes for the complete urea cycle that, in combination with urease, produces ammonia as an end product. Not only does the cockroach endosymbiont play an essential role in nutrient supply to the host, but also in the catabolic use of amino acids and nitrogen excretion, as strongly suggested by the stoichiometric analysis of the inferred metabolic network. Here, we explain the metabolic reasons underlying the enigmatic return of cockroaches to the ancestral ammonotelic state.

Major changes in microbial diversity and community composition across gut sections of a juvenile Panchlora cockroach.

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Erin A Gontang

Full Text Available Investigations of gut microbiomes have shed light on the diversity and genetic content of these communities, and helped shape our understanding of how host-associated microorganisms influence host physiology, behavior, and health. Despite the importance of gut microbes to metazoans, our understanding of the changes in diversity and composition across the alimentary tract, and the source of the resident community are limited. Here, using community metagenomics and 16S rRNA gene sequencing, we assess microbial community diversity and coding potential in the foregut, midgut, and hindgut of a juvenile Panchlora cockroach, which resides in the refuse piles of the leaf-cutter ant species Atta colombica. We found a significant shift in the microbial community structure and coding potential throughout the three gut sections of Panchlora sp., and through comparison with previously generated metagenomes of the cockroach's food source and niche, we reveal that this shift in microbial community composition is influenced by the ecosystems in which Panchlora sp. occurs. While the foregut is composed of microbes that likely originate from the symbiotic fungus gardens of the ants, the midgut and hindgut are composed of a microbial community that is likely cockroach-specific. Analogous to mammalian systems, the midgut and hindgut appear to be dominated by Firmicutes and Bacteroidetes with the capacity for polysaccharide degradation, suggesting they may assist in the degradation of dietary plant material. Our work underscores the prominence of community changes throughout gut microbiomes and highlights ecological factors that underpin the structure and function of the symbiotic microbial communities of metazoans.

Major changes in microbial diversity and community composition across gut sections of a juvenile Panchlora cockroach.

Science.gov (United States)

Gontang, Erin A; Aylward, Frank O; Carlos, Camila; Glavina Del Rio, Tijana; Chovatia, Mansi; Fern, Alison; Lo, Chien-Chi; Malfatti, Stephanie A; Tringe, Susannah G; Currie, Cameron R; Kolter, Roberto

2017-01-01

Investigations of gut microbiomes have shed light on the diversity and genetic content of these communities, and helped shape our understanding of how host-associated microorganisms influence host physiology, behavior, and health. Despite the importance of gut microbes to metazoans, our understanding of the changes in diversity and composition across the alimentary tract, and the source of the resident community are limited. Here, using community metagenomics and 16S rRNA gene sequencing, we assess microbial community diversity and coding potential in the foregut, midgut, and hindgut of a juvenile Panchlora cockroach, which resides in the refuse piles of the leaf-cutter ant species Atta colombica. We found a significant shift in the microbial community structure and coding potential throughout the three gut sections of Panchlora sp., and through comparison with previously generated metagenomes of the cockroach's food source and niche, we reveal that this shift in microbial community composition is influenced by the ecosystems in which Panchlora sp. occurs. While the foregut is composed of microbes that likely originate from the symbiotic fungus gardens of the ants, the midgut and hindgut are composed of a microbial community that is likely cockroach-specific. Analogous to mammalian systems, the midgut and hindgut appear to be dominated by Firmicutes and Bacteroidetes with the capacity for polysaccharide degradation, suggesting they may assist in the degradation of dietary plant material. Our work underscores the prominence of community changes throughout gut microbiomes and highlights ecological factors that underpin the structure and function of the symbiotic microbial communities of metazoans.

Evolutionary Convergence and Nitrogen Metabolism in Blattabacterium strain Bge, Primary Endosymbiont of the Cockroach Blattella germanica

Science.gov (United States)

López-Sánchez, Maria J.; Neef, Alexander; Peretó, Juli; Patiño-Navarrete, Rafael; Pignatelli, Miguel; Latorre, Amparo; Moya, Andrés

2009-01-01

Bacterial endosymbionts of insects play a central role in upgrading the diet of their hosts. In certain cases, such as aphids and tsetse flies, endosymbionts complement the metabolic capacity of hosts living on nutrient-deficient diets, while the bacteria harbored by omnivorous carpenter ants are involved in nitrogen recycling. In this study, we describe the genome sequence and inferred metabolism of Blattabacterium strain Bge, the primary Flavobacteria endosymbiont of the omnivorous German cockroach Blattella germanica. Through comparative genomics with other insect endosymbionts and free-living Flavobacteria we reveal that Blattabacterium strain Bge shares the same distribution of functional gene categories only with Blochmannia strains, the primary Gamma-Proteobacteria endosymbiont of carpenter ants. This is a remarkable example of evolutionary convergence during the symbiotic process, involving very distant phylogenetic bacterial taxa within hosts feeding on similar diets. Despite this similarity, different nitrogen economy strategies have emerged in each case. Both bacterial endosymbionts code for urease but display different metabolic functions: Blochmannia strains produce ammonia from dietary urea and then use it as a source of nitrogen, whereas Blattabacterium strain Bge codes for the complete urea cycle that, in combination with urease, produces ammonia as an end product. Not only does the cockroach endosymbiont play an essential role in nutrient supply to the host, but also in the catabolic use of amino acids and nitrogen excretion, as strongly suggested by the stoichiometric analysis of the inferred metabolic network. Here, we explain the metabolic reasons underlying the enigmatic return of cockroaches to the ancestral ammonotelic state. PMID:19911043

Home Sweet Home: How to Build a Madagascar Hissing Cockroach Habitat out of Recycled Materials

Science.gov (United States)

Wagler, Ron

2010-01-01

Madagascar hissing cockroaches (MHC) are amazing insects that can be an integral part of an effective science learning and teaching environment. MHCs have a fascinating social structure. They make excellent pets, teach students how to properly care for animals, and their large size adds to their "wow" factor. These characteristics make them unique…

CIRCADIAN CONTROL OF VISUAL INFORMATION-PROCESSING IN THE OPTIC LOBE OF THE GIANT COCKROACH BLABERUS-GIGANTEUS

NARCIS (Netherlands)

BULT, R; MASTEBROEK, HAK

1993-01-01

Extracellular spike activity from three different types of visual interneurons found in the optic lobe of the giant cockroach Blaberus giganteus was recorded. The spike rate of all three types of neurons fluctuated in a circadian manner in constant darkness (DD). Two types, so-called ''on'' neurons

Effective Stimulus Parameters for Directed Locomotion in Madagascar Hissing Cockroach Biobot.

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Jonathan C Erickson

Full Text Available Swarms of insects instrumented with wireless electronic backpacks have previously been proposed for potential use in search and rescue operations. Before deploying such biobot swarms, an effective long-term neural-electric stimulus interface must be established, and the locomotion response to various stimuli quantified. To this end, we studied a variety of pulse types (mono- vs. bipolar; voltage- vs. current-controlled and shapes (amplitude, frequency, duration to parameters that are most effective for evoking locomotion along a desired path in the Madagascar hissing cockroach (G. portentosa in response to antennal and cercal stimulation. We identified bipolar, 2 V, 50 Hz, 0.5 s voltage controlled pulses as being optimal for evoking forward motion and turns in the expected contraversive direction without habituation in ≈50% of test subjects, a substantial increase over ≈10% success rates previously reported. Larger amplitudes for voltage (1-4 V and current (50-150 μA pulses generally evoked larger forward walking (15.6-25.6 cm; 3.9-5.6 cm/s but smaller concomitant turning responses (149 to 80.0 deg; 62.8 to 41.2 deg/s. Thus, the radius of curvature of the initial turn-then-run locomotor response (≈10-25 cm could be controlled in a graded manner by varying the stimulus amplitude. These findings could be used to help optimize stimulus protocols for swarms of cockroach biobots navigating unknown terrain.

Role of tropomyosin as a cross-reacting allergen in sensitization to cockroach in patients from Martinique (French Caribbean island) with a respiratory allergy to mite and a food allergy to crab and shrimp

NARCIS (Netherlands)

Purohit, A.; Shao, J.; Degreef, J. M.; van Leeuwen, A.; van Ree, R.; Pauli, G.; de Blay, F.

2007-01-01

BACKGROUND: Tropomyosin has been described as cross-reacting allergen between mite, cockroach and shrimp. METHODS: In 13 patients with asthma and/or rhinitis sensitized to mite and/or German cockroach and presenting urticaria, oral allergy syndrome or angio-edema upon eating shrimp and/or crab, we

Identification of four Drosophila allatostatins as the cognate ligands for the Drosophila orphan receptor DAR-2

DEFF Research Database (Denmark)

Lenz, C; Williamson, M; Hansen, G N

2001-01-01

The allatostatins are generally inhibitory insect neuropeptides. The Drosophila orphan receptor DAR-2 is a G-protein-coupled receptor, having 47% amino acid residue identity with another Drosophila receptor, DAR-1 (which is also called dros. GPCR, or DGR) that was previously shown...... to be the receptor for an intrinsic Drosophila A-type (cockroach-type) allatostatin. Here, we have permanently expressed DAR-2 in CHO cells and found that it is the cognate receptor for four Drosophila A-type allatostatins, the drostatins-A1 to -A4. Of all the drostatins, drostatin-A4 (Thr...... weakly in the brain. The Drosophila larval gut also contains about 20-30 endocrine cells, expressing the gene for the drostatins-A1 to -A4. We suggest, therefore, that DAR-2 mediates an allatostatin (drostatin)-induced inhibition of gut motility. This is the first report on the permanent and functional...

Biogeography and Phylogeny of Wood-feeding Cockroaches in the Genus Cryptocercus

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Kiyoto Maekawa

2011-07-01

Full Text Available Subsocial, xylophagous cockroaches of the genus Cryptocercus exhibit a disjunct distribution, with representatives in mature montane forests of North America, China, Korea and the Russian Far East. All described species are wingless and dependent on rotting wood for food and shelter at all stages of their life cycle; consequently, their distribution is tied to that of forests and strongly influenced by palaeogeographical events. Asian and American lineages form distinct monophyletic groups, comprised of populations with complex geographic substructuring. We review the phylogeny and distribution of Cryptocercus, and discuss splitting events inferred from molecular data.

Leg Regrowth in Blaberus discoidalis (Discoid Cockroach following Limb Autotomy versus Limb Severance and Relevance to Neurophysiology Experiments.

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Timothy C Marzullo

Full Text Available Many insects can regenerate limbs, but less is known about the regrowth process with regard to limb injury type. As part of our neurophysiology education experiments involving the removal of a cockroach leg, 1 the ability of Blaberus discoidalis cockroaches to regenerate a metathoracic leg was examined following autotomy at the femur/trochanter joint versus severance via a transverse coxa-cut, and 2 the neurophysiology of the detached legs with regard to leg removal type was studied by measuring spike firing rate and microstimulation movement thresholds.First appearance of leg regrowth was after 5 weeks in the autotomy group and 12 weeks in the coxa-cut group. Moreover, regenerated legs in the autotomy group were 72% of full size on first appearance, significantly larger (p<0.05 than coxa-cut legs (29% of full size at first appearance. Regenerated legs in both groups grew in size with each subsequent molt; the autotomy-removed legs grew to full size within 18 weeks, whereas coxa-cut legs took longer than 28 weeks to regrow. Removal of the metathoracic leg in both conditions did not have an effect on mortality compared to matched controls with unmolested legs.Autotomy-removed legs had lower spontaneous firing rates, similar marked increased firing rates upon tactile manipulation of tibial barbs, and a 10% higher electrical microstimulation threshold for movement.It is recommended that neurophysiology experiments on cockroach legs remove the limb at autotomy joints instead of coxa cuts, as the leg regenerates significantly faster when autotomized and does not detract from the neurophysiology educational content.

Aromatic hexamerin subunit from adult female cockroaches (Blaberus discoidalis) : Molecular cloning, suppression by juvenile hormone, and evolutionary perspectives

NARCIS (Netherlands)

Jamroz, RC; Beintema, JJ; Stam, WT; Bradfield, JY

In an effort to identify several polypeptides that are strongly suppressed by juvenile hormone (JH) in fat body of adult female Blaberus discoidalis cockroaches, we have cloned a cDNA representing a polypeptide member of the hexamerin family of arthropod serum proteins. The deduced primary

The evolutionary transition from subsocial to eusocial behaviour in Dictyoptera: phylogenetic evidence for modification of the "shift-in-dependent-care" hypothesis with a new subsocial cockroach.

Science.gov (United States)

Pellens, Roseli; D'Haese, Cyrille A; Bellés, Xavier; Piulachs, Maria-Dolors; Legendre, Frédéric; Wheeler, Ward C; Grandcolas, Philippe

2007-05-01

Cockroaches have always been used to understand the first steps of social evolution in termites because they are close relatives with less complex and integrated social behaviour. Termites are all eusocial and ingroup comparative analysis would be useless to infer the origin of their social behaviour. The cockroach genus Cryptocercus was used as a so-called "prototermite" model because it shows key-attributes similar to the termites (except Termitidae): wood-feeding, intestinal flagellates and subsocial behaviour. In spite of these comparisons between this subsocial cockroach and eusocial termites, the early and remote origin of eusocial behaviour in termites is not well understood yet and the study of other relevant "prototermite" models is however needed. A molecular phylogenetic analysis was carried out to validate a new "prototermite" model, Parasphaeria boleiriana which shows a peculiar combination of these key-attributes. It shows that these attributes of Parasphaeria boleiriana have an independent origin from those of other wood-eating cockroaches and termites. The case of P. boleiriana suggests that a short brood care was selected for with life on an ephemeral wood resource, even with the need for transmission of flagellates. These new phylogenetic insights modify evolutionary hypotheses, contradicting the assumption made with Cryptocercus model that a long brood care is necessary for cooperation between broods in the "shift-in-dependent-care" hypothesis. An ephemeral wood resource is suggested to prompt generation overlap and the evolution of cooperation, even if brood care is shortened.

Larval serum proteins of the gypsy moth, Lymantria dispar: Allometric changes during development suggest several functions for arylphorin and lipophorin

International Nuclear Information System (INIS)

Karpells, S.T.

1989-01-01

Storage proteins are the major nutritive intermediates in insects and although the serum storage proteins are relatively well studied, definitive roles for many of them have yet to be established. To further characterize their roles in development and to establish quantitative baselines for future studies, two serum proteins, arylphorin (Ap) and lipophorin (Lp), of the gypsy moth, Lymantria dispar, were studied. Ap and Lp, isolated from larval hemolymph, were partially characterized biochemically and immunologically. Hemolymph concentrations throughout larval development were determined using quantitative immunoelectrophoresis and absolute hemolymph amounts of protein were determined by measuring hemolymph volume. Cyclic fluctuations in hemolymph concentrations of Ap in particular correlated with each molting cycle and an increase in Lp levels just prior to pupation suggest a metamorphic change in the role or demand for the protein. Sexual dimorphism in protein concentrations are explained in part by the sexual dimorphism in the number of larval instars. In fact, an additional instar of Ap accumulation in the female gypsy moth is suggested to compensate for the lack of a female-specific storage protein in this species. The last two days of each instar were found to be the optimum time to sample protein concentration with minimum variance. Allometric relationships among Ap accumulation, Lp accumulation and weight gain were uncovered. Ap labelled with [ 14 C]-N-ethylmaleimide was shown to be incorporated into newly synthesized cuticle and setae during a larval-larval molt. The antiserum developed against L. dispar Ap was used to identify the Ap of Trichoplusia in and study Ap titers in parasitized T. in larvae. The antiserum was also used to determine the immunological relatedness of 5 species of Lepidoptera

A strategy for solubilizing delipidated apolipoprotein with lysophosphatidylcholine and reconstitution with phosphatidylcholine

International Nuclear Information System (INIS)

Kawooya, J.K.; Wells, M.A.; Law, J.H.

1989-01-01

The apolipoproteins of insect lipophorin were dissociated in guanidinium chloride and isolated by gel permeation chromatography. Over 98% of the total lipid in lipophorin was associated with apolipophorin I (apoLp-I), thus suggesting this apolipoprotein to be the lipid binding component of the particle. ApoLp-I was delipidated with ethanol/ether and solubilized in buffer that contained radioactive lysophosphatidylcholine ([ 3 H]LPC) above the critical micellar concentration. Sonic irradiation of radioactive phosphatidylcholine ([ 14 C]PC) with [ 3 H]LPC-solubilized apoLp-I at a molar ratio of 318 resulted in reconstituted lipophorin I (RLp-I). [ 3 H]LPC was bound to fatty acid free bovine serum albumin and was separated from RLp-I by density gradient ultracentrifugation and gel permeation chromatography. Negatively stained RLp-I particles were quasispherical with an average radius of 55 angstrom, and their overall morphology and secondary structure were similar to those of native hemolymph lipophorin. The RLp-I particle had a ρ = 1.137 g/mL, a M r ∼ 5.2 x 10 5 , and a [ 14 C]PC:apoLp-I molar ratio of 308. From the compositional analysis, molecular size, trypsinization, and lipolysis with phospholipase A 2 , the authors concluded that each RLp-I particle contained one molecule of apoLp-I and a monomolecular layer of [ 14 C]PC. When injected into the hemolymph of adult moths in vivo, RLp-I was loaded with lipid, as judged by a decrease in its density both in the presence and in the absence of adipokinetic hormone. The similarities in morphology and immunology of RLp-I and native lipophorin, together with the ability of RLp-I to load lipid, suggest that reconstituted lipophorins may serve as models to probe lipophorin structure and function

Rediscovered and new perisphaerine cockroaches from SW China with a review of subfamilial diagnosis (Blattodea: Blaberidae).

Science.gov (United States)

Li, Xin-Ran; Wang, Li-Li; Wang, Zong-Qing

2018-04-17

The taxonomic records of Chinese perisphaerine cockroaches were scattered in literature, and therefore a dedicated study is desired to update our knowledge. This paper reviews the subfamilial diagnosis and Chinese species, mostly from southwestern China. We provide high-definition habitus photos and drawings, the latter emphasizes the genitalia of both sexes, which are generalized with diagrams, abstracted from specimens examined. A total of 18 species are recorded in four genera, including Perisphaerus, or pill cockroach, the type genus of the subfamily. Two new genera and three new species are proposed: Achatiblatta achates gen. sp. nov., Frumentiforma frumentiformis gen. sp. nov., and Pseudoglomeris montana sp. nov.. Pseudoglomeris has five new junior synonyms: Corydidarum, Trichoblatta, Kurokia, Glomerexis, and Glomeriblatta; the following combinations are thus revived or new: Ps. aerea comb. nov., Ps. angustifolia comb. nov., Ps. beybienkoi comb. nov., Ps. fallax comb. nov., Ps. magnifica comb. rev., Ps. montshadskii comb. nov., Ps. nigra comb. nov., Ps. sculpta comb. nov., Ps. semisulcata comb. rev., Ps. tibetana comb. nov., and Ps. valida moderata comb. nov.. The following species are revalidated and combinations revived: Pe. pygmaeus comb. rev., Ps. dubia comb. sp. rev., and Ps. planiuscla comb. sp. rev.

Cellular elements for seeing in the dark: voltage-dependent conductances in cockroach photoreceptors

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Salmela Iikka

2012-08-01

Full Text Available Abstract Background The importance of voltage-dependent conductances in sensory information processing is well-established in insect photoreceptors. Here we present the characterization of electrical properties in photoreceptors of the cockroach (Periplaneta americana, a nocturnal insect with a visual system adapted for dim light. Results Whole-cell patch-clamped photoreceptors had high capacitances and input resistances, indicating large photosensitive rhabdomeres suitable for efficient photon capture and amplification of small photocurrents at low light levels. Two voltage-dependent potassium conductances were found in the photoreceptors: a delayed rectifier type (KDR and a fast transient inactivating type (KA. Activation of KDR occurred during physiological voltage responses induced by light stimulation, whereas KA was nearly fully inactivated already at the dark resting potential. In addition, hyperpolarization of photoreceptors activated a small-amplitude inward-rectifying (IR current mediated at least partially by chloride. Computer simulations showed that KDR shapes light responses by opposing the light-induced depolarization and speeding up the membrane time constant, whereas KA and IR have a negligible role in the majority of cells. However, larger KA conductances were found in smaller and rapidly adapting photoreceptors, where KA could have a functional role. Conclusions The relative expression of KA and KDR in cockroach photoreceptors was opposite to the previously hypothesized framework for dark-active insects, necessitating further comparative work on the conductances. In general, the varying deployment of stereotypical K+ conductances in insect photoreceptors highlights their functional flexibility in neural coding.

Suboptimal nutrient balancing despite dietary choice in glucose-averse German cockroaches, Blattella germanica.

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Jensen, Kim; Schal, Coby; Silverman, Jules

2015-10-01

Insects have evolved fine-tuned gustatory and post-ingestive physiological mechanisms that enable them to self-select an optimal composition of macronutrients. Their ability to forage optimally among multiple food sources and maximize fitness parameters depends on their ability not only to taste and perceive the nutritional value of potential foods but also to avoid deleterious components; the strength of such avoidance should reflect the severity of the perceived hazard. In German cockroaches (Blattella germanica), glucose aversion has evolved in some populations in response to anthropogenic selection with glucose-containing insecticidal baits. In four feeding treatments, we gave newly eclosed glucose-averse female cockroaches free choice to feed from two artificial, nutritionally complementary foods varying in protein and carbohydrate composition, with glucose or fructose as the sole carbohydrate source in either food. After 6days of feeding, we measured diet consumption and the length of basal oocytes as an estimate of sexual maturation. The females did not compromise on their aversion to glucose in order to balance their protein and carbohydrate intake, and experienced lower sexual maturation rates as a consequence. Nutrient specific hunger via feedback mechanisms, and adjustments to gustatory sensitivity thus do not override the deterrence of glucose, likely due to strong selection against ingesting even small amounts of toxin associated with glucose in baits. In the absence of baits, glucose aversion would be expected to incur a fitness cost compared to wild-type individuals due to lower overall food availability but also to larger difficulty in attaining a nutritionally balanced diet. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transplantation immunity in the American cockroach, Periplaneta americana: the rejection of integumentary grafts from Blatta orientalis.

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Karp, R D; Meade, C C

1993-01-01

The results from several previous studies have indicated that the American cockroach is able to respond to integumentary xenografts, but doubt remained as to whether cockroaches could effectively discriminate between self and allogeneic differences. This was emphasized by the fact that while one study reported that Periplaneta americana responded to grafts donated by the closely related genus Blatta orientalis, the data reported elsewhere, using a different assay system, found no such reactivity. Since we have subsequently reported, using a direct histological assay, that Periplaneta can in fact recognize and destroy integumentary allografts, we initiated a study to hopefully sort out the enigma presented by previous data using Blatta as a transplant donor. Integument from Blatta orientalis was transplanted orthotopically onto Periplaneta americana, and at various time points post-transplant, scored histologically for the survival of the subcuticular epidermal layer. The results clearly demonstrated that Periplaneta reacted to the Blatta tissue, because approximately 82% of the grafts had the epidermal layer destroyed by day 7 posttransplant. The kinetics of the response to Blatta was more in line with our allograft data, which would be in agreement with other work indicating that the closer the donor and recipient are on the phylogenetic tree, the less intense the reactivity to the foreign transplant.

Site of water vapor absorption in the desert cockroach, Arenivaga investigata.

Science.gov (United States)

O'Donnell, M J

1977-01-01

The desert cockroach, Arenivaga investigata, can gain weight by absorption of water-vapor from unsaturated atmospheres above 82.5% relative humidity. Blocking the anus or the dorsal surface with wax does not prevent water vapor uptake, but interference with movements of the mouthparts or blocking the mouth with wax-prevents such uptake. Weight gains are associated with the protrusion from the mouth of two bladder-like extensions of the hypopharynx. During absorption these structures are warmer than the surrounding mouthparts, their surface temperature increasing with relative humidity. This suggests that the surfaces of the bladder-like structures function at least as sites for condensation of water vapor, but the precise location of its transfer into the hemolymph has not yet been identified. Images PMID:266217

Look at That!: Using Madagascar Hissing Cockroaches to Develop and Enhance the Scientific Inquiry Skill of Observation in Middle School Students

Science.gov (United States)

Wagler, Ron

2011-01-01

Middle school students can develop and enhance their observation skills by participating in teacher-guided scientific inquiry (NRC 1996) activities where they observe animals that tend to act in known, predictable ways. Madagascar hissing cockroaches ("Gromphadorhina portentosa") are one such animal. This article presents beginning, intermediate,…

Isolation and Identification of Two Novel Attractant Compounds from Chinese Cockroach (Eupolyphaga sinensis Walker by Combination of HSCCC, NMR and CD Techniques

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Bin Wu

2013-09-01

Full Text Available High-speed counter-current chromatography (HSCCC with a two-phase solvent system composed of n-hextane-ethyl acetate-methanol-water (1.5:1:1.5:1, v/v/v/v was applied to the isolation and purification of attractants from Chinese cockroach, Eupolyphaga sinensis Walker. Two new attractants with attractant activity towards the male insects were obtained from the extract sample in a one-step separation. Their purities were determined by HPLC. Subsequent MS, NMR and CD analyses have led to the characterization of (R-3-ethyl-6,8-dihydroxy-7-methyl-3,4-dihydroisochromen-1-one (1 and (R-6,8-dihydroxy-3,7-dimethyl-3,4-dihydroisochromen-1-one (2, two novel isocumarin type attractants. Based on these results, it is concluded that HSCCC is a viable separation method option for purifying insect attractants, while effectively maintaining the attracting activity of the isolates. This is the first attempt to apply counter-current chromatography technique to separate attractants from Chinese cockroach.

Potential of ultraviolet radiation for control of American cockroach populations

International Nuclear Information System (INIS)

Gingrich, J.B.; Pratt, J.J. Jr.; Mandels, G.R.

1977-01-01

Populations of Periplaneta americana (L.) were exposed for 8-20 week periods in specially designed rooms to 254 nm UV radiation at low intensity (50-115 ergs s -1 cm -2 ), high intensity (160-220 ergs s -1 cm -2 ), or to white light. The rooms contained tables and chairs to simulate occupied space, with food and water placed in positions exposed to UV radiation. 'General' irradiation (where the whole room was exposed to UV) at 115 ergs s -1 cm -2 and above was effective in producing high mortality in all stages except 8-10th instar nymphs and adults. 'Hot-spots' irradiation (where UV lamps were placed behind table and chair harborages) produced high mortality only in 1st-3rd instar nymphs which would result in slower elimination of a population. Crude aggregation pheromone was not successful in holding cockroaches close to radiation sources or substantially increasing mortality under the conditions of the experiments

[Cockroaches and co. The role of health pests as allergen source].

Science.gov (United States)

Raulf, M; Sander, I; Gonnissen, D; Zahradnik, E; Brüning, T

2014-05-01

In most of the cases health pests are carriers of pathogens or parasites which have a negative impact on human health or affect the health of other mammals. What is lesser known is that they can also act as allergens. Most of the health pests in this sense belong to the arthropods, such as cockroaches (Blattaria), mosquitos (Culiciformia), lice (Pediculus humanus corporis), fleas (Siphonaptera) and ticks (Argasidae). In the group of vertebrates rats (Rattus norvegicus and Rattus rattus), house mice (Mus musculus) and pigeons (Columba livia domestica) are also classified as health pests. Also storage pests which are not carriers of pathogens can induce secondary infestation with hygiene pests or molds and have an underestimated impact on human health. In this article selected examples of health pests and also storage pests as an allergen source are described, taking into account the sensitization prevalence and identified single allergens.

Hierarchical Genetic Analysis of German Cockroach (Blattella germanica) Populations from within Buildings to across Continents

Science.gov (United States)

Vargo, Edward L.; Crissman, Jonathan R.; Booth, Warren; Santangelo, Richard G.; Mukha, Dmitry V.; Schal, Coby

2014-01-01

Understanding the population structure of species that disperse primarily by human transport is essential to predicting and controlling human-mediated spread of invasive species. The German cockroach (Blattella germanica) is a widespread urban invader that can actively disperse within buildings but is spread solely by human-mediated dispersal over longer distances; however, its population structure is poorly understood. Using microsatellite markers we investigated population structure at several spatial scales, from populations within single apartment buildings to populations from several cities across the U.S. and Eurasia. Both traditional measures of genetic differentiation and Bayesian clustering methods revealed increasing levels of genetic differentiation at greater geographic scales. Our results are consistent with active dispersal of cockroaches largely limited to movement within a building. Their low levels of genetic differentiation, yet limited active spread between buildings, suggests a greater likelihood of human-mediated dispersal at more local scales (within a city) than at larger spatial scales (within and between continents). About half the populations from across the U.S. clustered together with other U.S. populations, and isolation by distance was evident across the U.S. Levels of genetic differentiation among Eurasian cities were greater than those in the U.S. and greater than those between the U.S. and Eurasia, but no clear pattern of structure at the continent level was detected. MtDNA sequence variation was low and failed to reveal any geographical structure. The weak genetic structure detected here is likely due to a combination of historical admixture among populations and periodic population bottlenecks and founder events, but more extensive studies are needed to determine whether signatures of global movement may be present in this species. PMID:25020136

Gas exchange patterns and water loss rates in the Table Mountain cockroach, Aptera fusca (Blattodea: Blaberidae).

Science.gov (United States)

Groenewald, Berlizé; Bazelet, Corinna S; Potter, C Paige; Terblanche, John S

2013-10-15

The importance of metabolic rate and/or spiracle modulation for saving respiratory water is contentious. One major explanation for gas exchange pattern variation in terrestrial insects is to effect a respiratory water loss (RWL) saving. To test this, we measured the rates of CO2 and H2O release ( and , respectively) in a previously unstudied, mesic cockroach, Aptera fusca, and compared gas exchange and water loss parameters among the major gas exchange patterns (continuous, cyclic, discontinuous gas exchange) at a range of temperatures. Mean , and per unit did not differ among the gas exchange patterns at all temperatures (P>0.09). There was no significant association between temperature and gas exchange pattern type (P=0.63). Percentage of RWL (relative to total water loss) was typically low (9.79±1.84%) and did not differ significantly among gas exchange patterns at 15°C (P=0.26). The method of estimation had a large impact on the percentage of RWL, and of the three techniques investigated (traditional, regression and hyperoxic switch), the traditional method generally performed best. In many respects, A. fusca has typical gas exchange for what might be expected from other insects studied to date (e.g. , , RWL and cuticular water loss). However, we found for A. fusca that expressed as a function of metabolic rate was significantly higher than the expected consensus relationship for insects, suggesting it is under considerable pressure to save water. Despite this, we found no consistent evidence supporting the conclusion that transitions in pattern type yield reductions in RWL in this mesic cockroach.

Fast and Powerful: Biomechanics and Bite Forces of the Mandibles in the American Cockroach Periplaneta americana.

Directory of Open Access Journals (Sweden)

Tom Weihmann

Full Text Available Knowing the functionality and capabilities of masticatory apparatuses is essential for the ecological classification of jawed organisms. Nevertheless insects, especially with their outstanding high species number providing an overwhelming morphological diversity, are notoriously underexplored with respect to maximum bite forces and their dependency on the mandible opening angles. Aiming for a general understanding of insect biting, we examined the generalist feeding cockroach Periplaneta americana, characterized by its primitive chewing mouth parts. We measured active isometric bite forces and passive forces caused by joint resistance over the entire mandibular range with a custom-built 2D force transducer. The opening angle of the mandibles was quantified by using a video system. With respect to the effective mechanical advantage of the mandibles and the cross-section areas, we calculated the forces exerted by the mandible closer muscles and the corresponding muscle stress values. Comparisons with the scarce data available revealed close similarities of the cockroaches' mandible closer stress values (58 N/cm2 to that of smaller specialist carnivorous ground beetles, but strikingly higher values than in larger stag beetles. In contrast to available datasets our results imply the activity of faster and slower muscle fibres, with the latter becoming active only when the animals chew on tough material which requires repetitive, hard biting. Under such circumstances the coactivity of fast and slow fibres provides a force boost which is not available during short-term activities, since long latencies prevent a specific effective employment of the slow fibres in this case.

Paleocene origin of the cockroach families Blaberidae and Corydiidae: Evidence from Amur River region of Russia.

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Vršanský, Peter; Vidlička, L'Ubomír; Barna, Peter; Bugdaeva, Eugenia; Markevich, Valentina

2013-01-01

Morphna paleo sp. n., the earliest winged representative of any living cockroach genus and the earliest representative of the family Blaberidae, is described from the Danian Arkhara-Boguchan coal mine in the Amur River region (Russian Far East). The branched Sc and A suggest Ectobiidae (=Blattellidae) probably is not the ancestral family because Blaberidae were derived directly from the extinct family Mesoblattindae. The associated Danian locality Belaya Gora yielded Ergaula stonebut sp. n., the earliest record of the family Corydiidae. Both species belong to genera codominant in the Messel locality, thus validating their dominance in early Cenozoic assemblages.

Dietary choice for a balanced nutrient intake increases the mean and reduces the variance in the reproductive performance of male and female cockroaches.

Science.gov (United States)

Bunning, Harriet; Bassett, Lee; Clowser, Christina; Rapkin, James; Jensen, Kim; House, Clarissa M; Archer, Catharine R; Hunt, John

2016-07-01

Sexual selection may cause dietary requirements for reproduction to diverge across the sexes and promote the evolution of different foraging strategies in males and females. However, our understanding of how the sexes regulate their nutrition and the effects that this has on sex-specific fitness is limited. We quantified how protein (P) and carbohydrate (C) intakes affect reproductive traits in male (pheromone expression) and female (clutch size and gestation time) cockroaches (Nauphoeta cinerea). We then determined how the sexes regulate their intake of nutrients when restricted to a single diet and when given dietary choice and how this affected expression of these important reproductive traits. Pheromone levels that improve male attractiveness, female clutch size and gestation time all peaked at a high daily intake of P:C in a 1:8 ratio. This is surprising because female insects typically require more P than males to maximize reproduction. The relatively low P requirement of females may reflect the action of cockroach endosymbionts that help recycle stored nitrogen for protein synthesis. When constrained to a single diet, both sexes prioritized regulating their daily intake of P over C, although this prioritization was stronger in females than males. When given the choice between diets, both sexes actively regulated their intake of nutrients at a 1:4.8 P:C ratio. The P:C ratio did not overlap exactly with the intake of nutrients that optimized reproductive trait expression. Despite this, cockroaches of both sexes that were given dietary choice generally improved the mean and reduced the variance in all reproductive traits we measured relative to animals fed a single diet from the diet choice pair. This pattern was not as strong when compared to the single best diet in our geometric array, suggesting that the relationship between nutrient balancing and reproduction is complex in this species.

Molecular cloning of a functional allatostatin gut/brain receptor and an allatostatin preprohormone from the silkworm Bombyx mori

DEFF Research Database (Denmark)

Secher, Thomas; Lenz, C; Cazzamali, G

2001-01-01

in the DAR-1 and DAR-2 genes, showing that the three receptors are not only structurally but also evolutionarily related. Furthermore, we have cloned a Bombyx allatostatin preprohormone that contains eight different A-type allatostatins. Chinese hamster ovary cells permanently transfected with BAR DNA react......The cockroach-type or A-type allatostatins are inhibitory insect neuropeptides with the C-terminal sequence Tyr/Phe-X-Phe-Gly-Leu-NH(2). Here, we have cloned an A-type allatostatin receptor from the silkworm Bombyx mori (BAR). BAR is 361 amino acid residues long, has seven transmembrane domains....... Northern blots and quantitative reverse transcriptase-polymerase chain reaction of different larval tissues show that BAR mRNA is mainly expressed in the gut and to a much lesser extent in the brain. To our knowledge, this is the first report on the molecular cloning and functional expression of an insect...

MICROBIAL LOAD AND MULTIPLE DRUG RESISTANCE OF PATHOGENIC BACTERIA ISOLATED FROM FEACES AND BODY SURFACES OF COCKROACHES IN AN URBAN AREA OF SOUTHWESTERN NIGERIA

Directory of Open Access Journals (Sweden)

Monsuru Adebayo Adeleke

2012-06-01

Full Text Available This study investigates the microbial load and antibiotic susceptibility pattern of pathogenic bacteria isolated from the faeces and body surfaces of cockroaches in Osogbo, Southwestern Nigeria. The cockroaches collected from residential areas and hospital vicinities were screened for microbial load and antibiotic susceptibility pattern using standard protocols. A total of twenty- three microorganisms namely Klebsiella aerogenes, Bacillius cereus, Proteus spp, Staphyloccocus aureus, S. saprophyticus, Enteroccocus faecalis, Staphylococus epididermis, E. coli, Listeria monoctogene, Proteus mirabilis, Citrobacter species, Pseudomonas aeruginosa, Psuedomonas species, Seretia mensence, Candida albicans, Candida spp., Aspergilius spp., A. flavus, A. fumigates, Mucor species and Penicilium species were isolated. The microbial load of the microorganisms was significantly higher in the isolates from hospital as compared with the residential area (p<0.05 with the exception of Canidida species, Mucor and Penicillium which had higher or equal microbial load at the residential areas. All the pathogenic bacteria isolated had multiple resistance to antibiotics most importantly, Ampicillin, Augumentin, Amoxicillin and Septrin (30μg. Efforts geared towards controlling the insects will be indispensable in curbing the wide spread of multi-drug resistant pathogens in the study area.

In silico epitope prediction, expression and functional analysis of Per a 10 allergen from the American cockroach

Science.gov (United States)

Tong, Xunliang; Guo, Miao; Jin, Min; Chen, Hao; Li, Yanming; Wei, Ji-Fu

2016-01-01

Cockroach (CR) allergies caused by the American cockroach hyave been recognized to be repsonsible for IgE-mediated type I hypersensitivity worldwide. Per a 10 is one of the recognized main allergens of the American CR. In a previous study, we examined another American CR allergen, Per a 9 in patients with CR allergies and examined epitope sequences in this allergen. In the present study, we aimed to examine epitope sequences in the Per a 10 allergen. for this purpose, the Per a 10 gene was cloned and expressed in Escherichia coli (E. coli) systems. Our results revealed that 9 out of 16 (56.3%) sera from patients with American CR allergies reacted to Per a10, as assessed by ELISA, confirming that Per a 10 is a major allergen of the American CR. Our results also revealed that the expression of CD63 and CCR3 on passively sensitized basophils (obtained sera of patients with American CR allergies) was increased by approximately 2.3-fold, indicating that recombinant Per a 10 is functionally active. In addition, 3 immunoinformatics tools, namely the DNAStar Protean system, the Bioinformatics Predicted Antigenic Peptides (BPAP) system and the BepiPred 1.0 server were used to predict the peptides and the results revealed 8 peptides (2–12, 55–67, 98–120, 125–133, 149–160, 170–182, 201–208 and 223–227) as potential B cell epitopes of the Per a 10 allergen. Moreover, Per a 10 was predicted to have 3 T cell epitope sequences, namely 83–92, 139–147 and 162–170. The findings of our study on the CR allergen may prove to be useful in the development of peptide-based vaccine for the prevention and/or treatment of CR allergies. PMID:27840898

An augmented reality system validation for the treatment of cockroach phobia.

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Bretón-López, Juani; Quero, Soledad; Botella, Cristina; García-Palacios, Azucena; Baños, Rosa Maria; Alcañiz, Mariano

2010-12-01

Augmented reality (AR) is a new technology in which various virtual elements are incorporated into the user's perception of the real world. The most significant aspect of AR is that the virtual elements add relevant and helpful information to the real scene. AR shares some important characteristics with virtual reality as applied in clinical psychology. However, AR offers additional features that might be crucial for treating certain problems. An AR system designed to treat insect phobia has been used for treating phobia of small animals, and positive preliminary data about the global efficacy of the system have been obtained. However, it is necessary to determine the capacity of similar AR systems and their elements that are designed to evoke anxiety in participants; this is achieved by testing the correspondence between the inclusion of feared stimuli and the induction of anxiety. The objective of the present work is to validate whether the stimuli included in the AR-Insect Phobia system are capable of inducing anxiety in six participants diagnosed with cockroach phobia. Results support the adequacy of each element of the system in inducing anxiety in all participants.

[Effect of population density on enzymatic activity of antioxidative and phenol oxidase systems of imagoes and nymphs of the marble cockroach Nauphoeta cinerea].

Science.gov (United States)

Murzagulov, G S; Saltykova, E S; Gaĭfullina, L R; Nikolenko, A G

2013-01-01

The work deals with effect of density of population on functional activity of components pf protective system of adult individuals and nymphs of the marble cockroach. The resistance of individuals has been noted to decrease both at individual maintenance and under conditions of overpopulation. Changes in activities of enzymes of antioxidative and phenoloxidase systems are studied ion the insect hemolymph and intestine. Possible consequences of isolation and overpopulation are discussed both for stability and for individual development.

Establishing health standards for indoor foreign proteins related to asthma: Dust mite, cat and cockroach

Energy Technology Data Exchange (ETDEWEB)

Platts-Mills, T.A.E.; Chapman, M.D.; Pollart, S.M.; Heymann, P.W.; Luczynska, C.M. (Univ. of Virginia, Charlottesville (United States))

1990-01-01

There is no doubt that a large number of individuals become allergic to foreign proteins that are predominantly or exclusively present indoors. In each case this immune response can be demonstrated either by immediate skin test responses or by measuring serum IgE antibodies. It has also been obvious for some time that patients presenting with asthma, perennial rhinitis and atopic dermatitis have an increased prevalence of IgE antibodies to these indoor allergens. More recently several epidemiological surveys have suggested that both mite exposure and IgE antibodies are important risk factors for asthma. The present situation is that assays have been developed capable of measuring the presence of mite, cockroach and cat allergens in house dust. Further clinical studies will be necessary to test the proposed standards for mite allergens and to define risk levels for other allergens.

Synergistic effect of some essential oils on toxicity and knockdown effects, against mosquitos, cockroaches and housefly

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Idin Zibaee

2015-12-01

Full Text Available The toxicity and knockdown effect of Eucalyptus globulus, Rosmarinus officinalis essential oils and their mixed formulation on Periplaneta Americana (L., Blattella germanica (L., Supella longipalpa, Culex pipiens, Anopheles stephensi and Musca domestica were evaluated in a series of laboratory experiments. In all bioassay five different doses (0.625, 1.25, 2.5, 5 and 10% were used by filter paper (cm2 and aerosol (cm3 bioassay methods, all essential oils was toxic to cockroaches, mosquitos and housefly species the lowest and the highest LC50 belong to mixed formulation on B. germanica (LC50 6.1 and E. globulus on P. americana (LC50 27.7 respectively. In continuous exposure experiments, Mortality (LT50 values for cockroaches ranged from 1403.3 min with 0.625% E. globulus (for P. americana to 2.2 min with 10% mixed formulation for A. stephensi. The KT50 values ranged from 0.1 to 1090.8 min for 10% and 0.625 for mixed formulation and R. officinalis respectively. The mortality after 24 h for mixed formulation was 100% but for single essential oils ranged from 81.5 to 98.3 for P. americana treated with R. officinalis and A. stephensi treated with E. globulus respectively. Studies on persistence of essential oils on impregnated paper revealed that it has more adulticidal activity for longer period at low storage temperature. Gas chromatographic-mass spectrometric analysis of essential oil showed 14 and 16 peaks for E. globules and R. officinalis respectively. α-Pinene (39.8%, 1, 8-Cineole (13.2%, Camphene (9.1% and Borneol (3.7% were present in major amounts for R. officinalis and 1,8-Cineole (31.4%, α-Pinene (15.3%, d-Limonene (9.7% and α-Terpinolen (5.3% were present in major amounts for E. globulus respectively. Our results showed that two surveyed essential oils has compatible with synergistic effect on various insect species, furthermore it is useful for applying as integrated pest management tool for studied insects management, especially in

Deltamethrin-resistant German Cockroaches Are Less Sensitive to the Insect Repellents DEET and IR3535 than Non-resistant Individuals.

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Mengoni, Sofía L; Alzogaray, Raúl A

2018-04-02

The German cockroach, Blattella germanica (L.) (Blattodea: Blattellidae), is a serious worldwide pest with a considerable economical and sanitary impact. It is mainly controlled by the application of synthetic insecticides, but repeated use of these substances has promoted the appearance of resistance in cockroach populations throughout the world. The aim of this study was to compare the behavior of deltamethrin-susceptible (CIPEIN colony) and deltamethrin-resistant (JUBA and VGBA colonies) first instar nymphs exposed to the repellents N,N-diethyl-3-methylbenzamide (DEET) and ethyl 3-[acetyl(butyl)amino]propanoate (IR3535). Firstly, the behavior of the nymphs was assessed in an experimental arena in the absence of repellents. The parameters Distance Traveled, Velocity, Mobility Time, and Time Spent (in each half of the arena) were quantified using an image analyser, and showed that the behavior elicited by the three colonies was similar. After this, the behavior of the nymphs was quantified in an arena, half of which had been treated with repellent. The repellency of DEET increased as a linear function of log concentration for the three colonies. DEET elicited repellency as from a concentration of 97.49 µg/cm2 for the CIPEIN and JUBA colonies and 194.98 µg/cm2 for the VGBA colony. The repellency of IR3535 was weaker and started at a concentration of 389.96 µg/cm2 for the CIPEIN colony, 779.92 μg/cm2 for JUBA, and 1559.84 μg/cm2 for VGBA . Finally, nymphs were exposed to 3:1, 1:1, and 1:3 DEET:IR3535 mixtures, and a synergistic effect was observed only in the CIPEIN colony.

dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses.

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Lim, Sangho; Ho Sohn, Jung; Koo, Ja-Hyun; Park, Jung-Won; Choi, Je-Min

2017-08-04

German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma.

Calcium pathways such as cAMP modulate clothianidin action through activation of α-bungarotoxin-sensitive and -insensitive nicotinic acetylcholine receptors.

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Calas-List, Delphine; List, Olivier; Quinchard, Sophie; Thany, Steeve H

2013-07-01

Clothianidin is a neonicotinoid insecticide developed in the early 2000s. We have recently demonstrated that it was a full agonist of α-bungarotoxin-sensitive and -insensitive nicotinic acetylcholine receptors expressed in the cockroach dorsal unpaired median neurons. Clothianidin was able to act as an agonist of imidacloprid-insensitive nAChR2 receptor and internal regulation of cAMP concentration modulated nAChR2 sensitivity to clothianidin. In the present study, we demonstrated that cAMP modulated the agonist action of clothianidin via α-bungarotoxin-sensitive and insensitive receptors. Clothianidin-induced current-voltage curves were dependent to clothianidin concentrations. At 10 μM clothianidin, increasing cAMP concentration induced a linear current-voltage curve. Clothianidin effects were blocked by 0.5 μM α-bungarotoxin suggesting that cAMP modulation occurred through α-bungarotoxin-sensitive receptors. At 1 mM clothianidin, cAMP effects were associated to α-bungarotoxin-insensitive receptors because clothianidin-induced currents were blocked by 5 μM mecamylamine and 20 μM d-tubocurarine. In addition, we found that application of 1mM clothianidin induced a strong increase of intracellular calcium concentration. These data reinforced the finding that calcium pathways including cAMP modulated clothianidin action on insect nicotinic acetylcholine receptors. We proposed that intracellular calcium pathways such as cAMP could be a target to modulate the mode of action of neonicotinoid insecticides. Copyright © 2013 Elsevier Inc. All rights reserved.

Isolation and partial characterization of a second myotropic peptide from the hindgut of the cockroach, Leucophaea maderae.

Science.gov (United States)

Holman, G M; Cook, B J

1983-01-01

Proctolin and a second myotropic peptide were extracted from the hindgut of the cockroach Leucophaea maderae with methanol-water-acetic acid (90:9:1). The two peptides were easily separated by HPLC on a mu-Bondapak-phenyl column. Like proctolin, the second peptide was heat stable and was inactivated by the exopeptidases aminopeptidase M and carboxypeptidase Y. The response of the isolated hindgut to the new peptide was distinguishable from the response to proctolin by the following features: (a) a longer interval following application (1-4 min) to reach a maximum contraction, and (b) a much larger amplitude for single phasic contractions. Like proctolin, the new peptide could cause a protracted stimulation of the hindgut for more than 2 hr.

Regulatory natural killer cell expression in atopic childhood asthma

African Journals Online (AJOL)

Ehab

by different types of NK cells. Keywords: Natural killer, regulatory, asthma, children, allergy. ... aspergillus, cockroach, cat epithelia, and pollens) as well as positive histamine ..... also relied on detecting surface receptors for recognizing NK and ...

Transcriptome analysis and RNA interference of cockroach phototransduction indicate three opsins and suggest a major role for TRPL channels

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Andrew S French

2015-07-01

Full Text Available Our current understanding of insect phototransduction is based on a small number of species, but insects occupy many different visual environments. We created the retinal transcriptome of a nocturnal insect, the cockroach, Periplaneta americana to identify proteins involved in the earliest stages of compound eye phototransduction, and test the hypothesis that different visual environments are reflected in different molecular contributions to function. We assembled five novel mRNAs: two green opsins, one UV opsin, and one each TRP and TRPL ion channel homologs. One green opsin mRNA (pGO1 was 100-1000 times more abundant than the other opsins (pGO2 and pUVO, while pTRPL mRNA was 10 times more abundant than pTRP, estimated by transcriptome analysis or quantitative PCR (qPCR. Electroretinograms were used to record photoreceptor responses. Gene-specific in vivo RNA interference (RNAi was achieved by injecting long (596-708 bp double-stranded RNA into head hemolymph, and verified by qPCR. RNAi of the most abundant green opsin reduced both green opsins by more than 97% without affecting UV opsin, and gave a maximal reduction of 75% in ERG amplitude seven days after injection that persisted for at least 19 days. RNAi of pTRP and pTRPL genes each specifically reduced the corresponding mRNA by 90%. Electroretinogram reduction by pTRPL RNAi was slower than for opsin, reaching 75% attenuation by 21 days, without recovery at 29 days. pTRP RNAi attenuated ERG much less; only 30% after 21 days. Combined pTRP plus pTRPL RNAi gave only weak evidence of any cooperative interactions. We conclude that silencing retinal genes by in vivo RNAi using long dsRNA is effective, that visible light transduction in Periplaneta is dominated by pGO1, and that pTRPL plays a major role in cockroach phototransduction.

Laboratory Evaluation of Toxicity of Insecticide Formulations from Different Classes against American Cockroach (Dictyoptera: Blattidae.

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Ruhma Syed

2014-06-01

Full Text Available The present study was designed to investigate the insecticidal efficacy of four different classes of insecticides: pyrethroids, organophosphates, phenyl-pyrazoles and neo-nicotenoids. One representative chemical from each class was selected to compare the toxicity: deltamethrin from pyrethroids, Dichlorovinyl Dimethyl Phosphate (DDVP from organophosphates, fipronil from phenyl-pyrazoles and imidacloprid from neo-nicotenoids. The objective of this study was to determine which of these insecticides were most effective against American cockroach.These insecticides were tested for their LC50 values against Periplaneta americana under topical bioassay method, using different concentrations for each chemical.Fipronil 2.5% EC was highly effective at all concentrations applied, while DDVP 50% EC was least toxic amongst all. One way analysis of variance confirmed significant differences between mortality of P. americana and different concentrations applied (P< 0.05.Locality differentiation is an important factor in determining the range of resistance between various localities, as all three localities behaved differently in terms of their levels of resistance.

Flight metabolism in Panstrongylus megistus (Hemiptera: Reduviidae): the role of carbohydrates and lipids.

Science.gov (United States)

Canavoso, Lilián E; Stariolo, Raúl; Rubiolo, Edilberto R

2003-10-01

The metabolism of lipids and carbohydrates related to flight activity in Panstrongylus megistus was investigated. Insects were subjected to different times of flight under laboratory conditions and changes in total lipids, lipophorin density and carbohydrates were followed in the hemolymph. Lipids and glycogen were also assayed in fat body and flight muscle. In resting insects, hemolymph lipids averaged 3.4 mg/ml and significantly increased after 45 min of flight (8.8 mg/ml, P < 0.001). High-density lipophorin was the sole lipoprotein observed in resting animals. A second fraction with lower density corresponding to low-density lipophorin appeared in insects subjected to flight. Particles from both fractions showed significant differences in diacylglycerol content and size. In resting insects, carbohydrate levels averaged 0.52 mg/ml. They sharply declined more than twofold after 15 min of flight, being undetectable in hemolymph of insects flown for 45 min. Lipid and glycogen from fat body and flight muscle decreased significantly after 45 min of flight. Taken together, the results indicate that P. megistus uses carbohydrates during the initiation of the flight after which, switching fuel for flight from carbohydrates to lipids.

Flight metabolism in Panstrongylus megistus (Hemiptera: Reduviidae: the role of carbohydrates and lipids

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Lilián E Canavoso

2003-10-01

Full Text Available The metabolism of lipids and carbohydrates related to flight activity in Panstrongylus megistus was investigated. Insects were subjected to different times of flight under laboratory conditions and changes in total lipids, lipophorin density and carbohydrates were followed in the hemolymph. Lipids and glycogen were also assayed in fat body and flight muscle. In resting insects, hemolymph lipids averaged 3.4 mg/ml and significantly increased after 45 min of flight (8.8 mg/ml, P < 0.001. High-density lipophorin was the sole lipoprotein observed in resting animals. A second fraction with lower density corresponding to low-density lipophorin appeared in insects subjected to flight. Particles from both fractions showed significant differences in diacylglycerol content and size. In resting insects, carbohydrate levels averaged 0.52 mg/ml. They sharply declined more than twofold after 15 min of flight, being undetectable in hemolymph of insects flown for 45 min. Lipid and glycogen from fat body and flight muscle decreased significantly after 45 min of flight. Taken together, the results indicate that P. megistus uses carbohydrates during the initiation of the flight after which, switching fuel for flight from carbohydrates to lipids.

Variation in the mechanical properties of tracheal tubes in the American cockroach

International Nuclear Information System (INIS)

Becker, Winston R; Webster, Matthew R; De Vita, Raffaella; Socha, John J

2014-01-01

The insect cuticle serves the protective role of skin and the supportive role of the skeleton while being lightweight and flexible to facilitate flight. The smart design of the cuticle confers camouflage, thermo-regulation, communication, self-cleaning, and anti-wetting properties to insects. The mechanical behavior of the internal cuticle of the insect in tracheae remains largely unexplored due to their small size. In order to characterize the material properties of insect tracheae and understand their role during insect respiration, we conducted tensile tests on ring sections of tracheal tubes of American cockroaches (Periplaneta americana). A total of 33 ring specimens collected from 14 tracheae from the upper thorax of the insects were successfully tested. The ultimate tensile strength (22.6 ± 13.3 MPa), ultimate strain (1.57 ± 0.68%), elastic modulus (1740 ± 840 MPa), and toughness (0.175 ± 0.156 MJ m −3 ) were measured. We examined the high variance in mechanical properties statistically and demonstrated that ring sections excised from the same trachea exhibit comparable mechanical properties. Our results will form the basis for future studies aimed at determining the structure–function relationship of insect tracheal tubes, ultimately inspiring the design of multi-functional materials and structures. (technical note)

Actions of insecticides on the insect GABA receptor complex

International Nuclear Information System (INIS)

Bermudez, I.; Hawkins, C.A.; Taylor, A.M.; Beadle, D.J.

1991-01-01

The actions of insecticides on the insect gamma-aminobutyric acid (GABA) receptor were investigated using [35S]t-butylbicyclophosphorothionate [( 35S]TBPS) binding and voltage-clamp techniques. Specific binding of [35S]TBPS to a membrane homogenate derived from the brain of Locusta migratoria locusts is characterised by a Kd value of 79.3 ± 2.9 nM and a Bmax value of 1770 ± 40 fmol/mg protein. [35S]TBPS binding is inhibited by mM concentrations of barbiturates and benzodiazepines. In contrast dieldrin, ivermectin, lindane, picrotoxin and TBPS are inhibitors of [35S]TBPS binding at the nanomolar range. Bicuculline, baclofen and pyrethroid insecticides have no effect on [35S]TBPS binding. These results are similar to those obtained in electrophysiological studies of the current elicited by GABA in both Locusta and Periplaneta americana central neurones. Noise analysis of the effects of lindane, TBPS, dieldrin and picrotoxin on the cockroach GABA responses reveals that these compounds decrease the variance of the GABA-induced current but have no effect on its mean open time. All these compounds, with the exception of dieldrin, significantly decrease the conductance of GABA-evoked single current

A taxonomic study of the beetle cockroaches (Diploptera Saussure) from China, with notes on the genus and species worldwide (Blattodea: Blaberidae: Diplopterinae).

Science.gov (United States)

Li, Xinran; Wang, Zongqing

2015-09-14

Four taxa of beetle cockroaches (Diploptera Saussure, 1864) from South China are described and illustrated, viz., two new species D. elliptica sp. n. and D. naevus sp. n., one new subspecies D. nigrescens guani subsp. n. and one widespread known species D. punctata (Eschscholtz, 1822). The genus and known species from around the world are discussed based on types and other specimens. D. pulchra Anisyutkin, 2007 is now regarded as a junior synonym of D. bicolor Hanitsch, 1925. Whether the populations of D. punctata represent or not different species needs to be studied in the future. A key, a distribution map, and photos of species are provided.

Preparation and Identification of Per a 5 as a Novel American Cockroach Allergen

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Ji-Fu Wei

2014-01-01

Full Text Available Glutathione S-transferase (GST from various arthropods can elicit allergic reactions. In the present study, Per a 5, a GST, was cloned from American cockroach (CR and expressed in both baculovirus-infected insect cell (iPer a 5 and E. coli expression (bPer a 5 systems. The secondary structures were predicted to be 45.93 and 8.69% of α-helix β-sheets in iPer a 5 and 42.54 and 8.49% of α-helix and β-sheets in bPer a 5, respectively. It is found that 4 out of 16 (25% sera from American CR allergy patients reacted to both bPer a 9 and iPer a 9 as assessed by ELISA and Western blotting analysis, confirming that Per a 5 is not a major allergen of American CR. Induction of upregulated expression of CD63 and CCR3 on passively sensitized human basophils (sera from American CR allergy patients by approximately up to 4.5- and 3.2-fold indicates that iPer a 5 and bPer a 5 are functionally active. Recombinant Per a 5 (rPer a 5 should be a useful tool for studying and understanding the role of Per a 5 in CR allergy.

Evaluation of gamma irradiated essential oils to control stored-grain weevil, Sitophilus zeamais and cockroach, Blattella germanica

International Nuclear Information System (INIS)

Potenza, Marcos Roberto; Gomes, Davinni Habral Passini; Silvestre, Denise de Fatima; Da Silva, Rita de Cassia; Arthur, Valter

2004-01-01

Most of the essential oils have insecticidal activity and are alternatives to plant protection and urban pest control. The gamma radiation has been used to control microorganisms and insects in dehydrate herbs, spices, medicinal plants and other materials. This work aimed to evaluate the effect of irradiated essential oils as contact poison on Stored grain, weevil, Sitophilus zeamais and as stomach poison in cockroach, Blattella germanica. The bioassay with B. germanica demonstrated efficiency between 22.0 and 30.0% and between 30.0 and 42.0% respectively, to irradiated essential oils of E. citriodora and E. globulus and they demonstrated too repellency to the nymphs. The gamma radiation promoted changes in essential oils Eucalyptus citriodora and E. globulus and showed increased effectiveness on B. germanica nymphs besides a significative reduction of repellency. Gamma radiation thus interfered on behavior of some essential oils by increasing or reducing activating or inactivating their efficiency to pest control. (author)

Physiological Costs of Repetitive Courtship Displays in Cockroaches Handicap Locomotor Performance

Science.gov (United States)

Mowles, Sophie L.; Jepson, Natalie M.

2015-01-01

Courtship displays are typically thought to have evolved via female choice, whereby females select mates based on the characteristics of a display that is expected to honestly reflect some aspect of the male’s quality. Honesty is typically enforced by mechanistic costs and constraints that limit the level at which a display can be performed. It is becoming increasingly apparent that these costs may be energetic costs involved in the production of dynamic, often repetitive displays. A female attending to such a display may thus be assessing the physical fitness of a male as an index of his quality. Such assessment would provide information on his current physical quality as well as his ability to carry out other demanding activities, qualities with which a choosy female should want to provision her offspring. In the current study we use courtship interactions in the Cuban burrowing cockroach, Byrsotria fumigata to directly test whether courtship is associated with a signaler’s performance capacity. Males that had produced courtship displays achieved significantly lower speeds and distances in locomotor trials than non-courting control males. We also found that females mated more readily with males that produced a more vigorous display. Thus, males of this species have developed a strategy where they produce a demanding courtship display, while females choose males based on their ability to produce this display. Courtship displays in many taxa often involve dynamic repetitive actions and as such, signals of stamina in courtship may be more widespread than previously thought. PMID:26606147

Endocytosis of the major yolk proteins of the silkmoth, Hyalophora cecropia: Uptake kinetics and interactions

International Nuclear Information System (INIS)

Kulakosky, P.C.

1989-01-01

The oocytes of Lepidopteran insects take up several yolk proteins in defined proportions even though their relative availability in the hemolymph changes during the several days required to complete yolk formation in all the eggs. There are three hemolymph yolk precursors, vitellogenin, microvitellogenin and lipophorin; one precursor, paravitellogenin is produced in the ovary. The control mechanism for their proportional endocytosis is not known. In this thesis, the author describe the purification of all four proteins and the radiolabeling of the hemolymph precursors. The radiolabeled proteins were tested with an in vitro incubation system to assess the biological activity of the proteins and the reliability of the incubation methods. All of the labeled probes were transferred from the incubation medium to yolk spheres within the oocyte in a saturable, energy-dependent, and stage-specific manner. The rates of uptake were similar to the estimated rates of uptake in situ. The concentration dependence of in vitro uptake was investigated and found to be consistent with in situ concentrations and the composition of yolk in mature eggs. Two precursors, vitellogenin and lipophorin, competed for uptake indicating that they share a common binding site while the third, microvitellin, did not compete with the others. Though vitellogenin and lipophorin competed for uptake, only vitellogenin displayed the unique ability to increase the uptake rate of microvitellin and fluid in vitro

Transmembrane potential polarization, calcium influx, and receptor conformational state modulate the sensitivity of the imidacloprid-insensitive neuronal insect nicotinic acetylcholine receptor to neonicotinoid insecticides.

Science.gov (United States)

Bodereau-Dubois, Béatrice; List, Olivier; Calas-List, Delphine; Marques, Olivier; Communal, Pierre-Yves; Thany, Steeve H; Lapied, Bruno

2012-05-01

Neonicotinoid insecticides act selectively on insect nicotinic acetylcholine receptors (nAChRs). Recent studies revealed that their efficiency was altered by the phosphorylation/dephosphorylation process and the intracellular signaling pathway involved in the regulation of nAChRs. Using whole-cell patch-clamp electrophysiology adapted for dissociated cockroach dorsal unpaired median (DUM) neurons, we demonstrated that intracellular factors involved in the regulation of nAChR function modulated neonicotinoid sensitivity. DUM neurons were known to express two α-bungarotoxin-insensitive nAChR subtypes: nAChR1 and nAChR2. Whereas nAChR1 was sensitive to imidacloprid, nAChR2 was insensitive to this insecticide. Here, we demonstrated that, like nicotine, acetamiprid and clothianidin, other types of neonicotinoid insecticides, acted as agonists on the nAChR2 subtype. Using acetamiprid, we revealed that both steady-state depolarization and hyperpolarization affected nAChR2 sensitivity. The measurement of the input membrane resistance indicated that change in the acetamiprid-induced agonist activity was related to the receptor conformational state. Using cadmium chloride, ω-conotoxin GVIA, and (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-acetamide (LOE 908), we found that inhibition of calcium influx through high voltage-activated calcium channels and transient receptor potential γ (TRPγ) activated by both depolarization and hyperpolarization increased nAChR2 sensitivity to acetamiprid. Finally, using N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W7), forskolin, and cAMP, we demonstrated that adenylyl cyclase sensitive to the calcium/calmodulin complex regulated internal cAMP concentration, which in turn modulated TRPγ function and nAChR2 sensitivity to acetamiprid. Similar TRPγ-induced modulatory effects were also obtained when clothianidin was tested. These findings bring insights into the signaling pathway modulating

Standard metabolic rate is associated with gestation duration, but not clutch size, in speckled cockroaches Nauphoeta cinerea

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Natalie G. Schimpf

2012-09-01

Metabolic rate varies significantly between individuals, and these differences persist even when the wide range of biotic and abiotic factors that influence metabolism are accounted for. It is important to understand the life history implications of variation in metabolic rate, but they remain poorly characterised despite a growing body of work examining relationships between metabolism and a range of traits. In the present study we used laboratory-bred families (one sire to three dams of Nauphoeta cinerea (Olivier (speckled cockroaches to examine the relationship between standard metabolic rate (SMR and reproductive performance (number of offspring and gestation duration. We show that SMR is negatively associated with female gestation duration. Age at mating is negatively associated with gestation duration for females, and mass is negatively associated with the average gestation duration of the females a male was mated with. In addition to the results in the current literature, the results from the present study suggest that the association between metabolism and life history is more complex than simple relationships between metabolism and various fitness traits. Future work should consider longitudinal, ontogenetic as well as selective and quantitative genetic breeding approaches to fully examine the associations between metabolism and fitness.

Status of and future research on thermosensory processing

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Makoto eMizunami

2016-04-01

Full Text Available Thermosensation is critically important for survival of all animals. In the cockroach Periplaneta americana, thermoreceptor neurons on antennae and thermosensory interneurons in the antennal lobe have been characterized electrophysiologically, and recent studies using advanced transgenic technologies in the fruit fly Drosophila melanogaster have added much to the knowledge of these neurons, enabling us to discuss common principles of thermosensory processing systems in insects. Cockroaches and many other insects possess only one type of thermoreceptor neurons on antennae that are excited by cooling and inhibited by warming. In contrast, the antennae of fruit flies and other dipterans possess oppositely responding warm and cold receptor neurons. Despite differences in their thermoreceptive equipment, central processing of temperature information is much the same in flies and cockroaches. Axons of thermoreceptor neurons project to the margin of the antennal lobe and form glomeruli, from which cold, warm and cold-warm projection neurons originate, the last neurons being excited by both cooling and warming. Axons of antennal lobe thermosensory projection neurons of the antennal lobe terminate in three distinct areas of the protocerebrum, the mushroom body, lateral horn and posterior lateral protocerebrum, the last area also receiving termination of hygrosensory projection neurons. Such multiple thermosensory pathways may serve to control multiple forms of thermosensory behavior. Electrophysiological studies on cockroaches and transgenic approaches in flies are encouraged to complement each other for further elucidating general principles of thermosensory processing in the insect brain.

Human Plasma Very Low Density Lipoprotein Carries Indian Hedgehog

NARCIS (Netherlands)

Queiroz, Karla C. S.; Tio, Rene A.; Zeebregts, Clark J.; Bijlsma, Maarten F.; Zijlstra, Felix; Badlou, Bahram; de Vries, Marcel; Ferreira, Carmen V.; Spek, C. Arnold; Peppelenbosch, Maikel P.; Rezaee, Farhad

2010-01-01

Hedgehog is one of the major morphogens and fulfils critical functions in both the development and maintenance of the vasculature. Hedgehog is highly hydrophobic and its diffusion toward target tissues remains only partly understood. In Drosophila, hedgehog transport via lipophorins is relevant for

Human Plasma Very Low Density Lipoprotein Carries Indian Hedgehog

NARCIS (Netherlands)

Queiroz, Karla C. S.; Tio, Rene A.; Zeebregts, Clark J.; Bijlsma, Maarten F.; Zijlstra, Felix; Badlou, Bahram; de Vries, Marcel; Ferreira, Carmen V.; Spek, C. Arnold; Peppelenbosch, Maikel P.; Rezaee, Farhad

Hedgehog is one of the major morphogens and fulfils critical functions in both the development and maintenance of the vasculature. Hedgehog is highly hydrophobic and its diffusion toward target tissues remains only partly understood. In Drosophila, hedgehog transport via lipophorins is relevant for

Isolation and Purification of an Antibacterial Protein from Immune Induced Haemolymph of American Cockroach, Periplaneta americana

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Hamid Reza Basseri

2016-10-01

Full Text Available Background: Antimicrobial peptides play a role as effectors substances in the immunity of vertebrate and inverte­brate hosts. In the current study, antimicrobial peptide was isolated from the haemolymph of the American cock­roach, Periplaneta americana.Methods: Micrococcus luteus as Gram-positive bacteria and Escherichia coli as Gram-negative bacteria were candi­date for injection. Induction was done by injecting both bacteria into the abdominal cavity of two groups of cock­roaches separately. The haemolymphs were collected 24 hours after post injection and initially tested against both bacteria. Subsequently, the immune induced haemolymph was purified by high performance liquid chromatography (HPLC to separate the proteins responsible for the antibacterial activity.Results: The non-induced haemolymph did not show any activity against both bacteria whereas induced haemo­lymph exhibited high activity against M. luteus but did less against E. coli. Two fractions showed antibacterial activ­ity against M. luteus. Finally the molecular weight of the isolated antibacterial proteins were determined as 72 kDa and 62 kDa using SDS-PAGE.Conclusion: Induced haemolymph of American cockroaches has the ability to produce peptides to combat against Gram-positive bacteria when an immune challenge is mounted. Further work has to be done to sequence of the pro­tein, which it would be advantageous.

The cuticular hydrocarbons of the giant soil-burrowing cockroach Macropanesthia rhinoceros saussure (Blattodea: Blaberidae: Geoscapheinae): analysis with respect to age, sex and location.

Science.gov (United States)

Brown, W V; Rose, H A; Lacey, M J; Wright, K

2000-11-01

The cuticular hydrocarbons of a widespread species of soil-burrowing cockroach, Macropanesthia rhinoceros, have been sampled from most of its known geographical locations. Analysis of extracts from individual insects has enabled a study of differences within a population as well as among geographical locations. In the case of M. rhinoceros, except for newly hatched first-instar nymphs, variations in hydrocarbon composition among individuals of different cohorts of M. rhinoceros, based on age and sex, are no greater than those among individuals of a single cohort. Geographical populations of this species are variable in hydrocarbon composition unless they occur within a few kilometres of each other. A few populations showed very different hydrocarbon patterns but, in the absence of any correlating biological differences, it is uncertain whether this signifies the presence of otherwise unrecognizable sibling species or just extreme examples of the geographical variation characteristic of this group of insects.

Intersegmental coordination of cockroach locomotion: adaptive control of centrally coupled pattern generator circuits

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Einat eFuchs

2011-01-01

Full Text Available Animals’ ability to demonstrate both stereotyped and adaptive locomotor behavior is largely dependent on the interplay between centrally-generated motor patterns and the sensory inputs that shape them. We utilized a combined experimental and theoretical approach to investigate the relative importance of CPG interconnections vs. intersegmental afferents in the cockroach: an animal that is renowned for rapid and stable locomotion. We simultaneously recorded coxal levator and depressor motor neurons (MN in the thoracic ganglia of Periplaneta americana, while sensory feedback was completely blocked or allowed only from one intact stepping leg. In the absence of sensory feedback, we observed a coordination pattern with consistent phase relationship that shares similarities with a double tripod gait, suggesting central, feedforward control. This intersegmental coordination pattern was then reinforced in the presence of sensory feedback from a single stepping leg. Specifically, we report on transient stabilization of phase differences between activity recorded in the middle and hind thoracic MN following individual front-leg steps, suggesting a role for afferent phasic information in the coordination of motor circuits at the different hemiganglia. Data were further analyzed using stochastic models of coupled oscillators and maximum likelihood techniques to estimate underlying physiological parameters, such as uncoupled endogenous frequencies of hemisegmental oscillators and coupling strengths and directions. We found that descending ipsilateral coupling is stronger than ascending coupling, while left-right coupling in both the meso- and meta-thoracic ganglia appear to be symmetrical. We discuss our results in comparison with recent findings in stick insects that share similar neural and body architectures, and argue that the two species may exemplify opposite extremes of a fast-slow locomotion continuum, mediated through different intersegmental

Imidacloprid poisoning: a modern foe

OpenAIRE

Raminderpal Singh Sibia; Amith Kumar S; Sandipkumar Radheshyam Dhoot

2014-01-01

Imidacloprid is a relatively new insecticide in the chloronicotinyl nitroguanidine class. Imidacloprid has a wide variety of uses; it is used on cotton and vegetable crops, turf grass and ornamental plant products, in indoor and outdoor cockroach control products and in termite control products. Imidacloprid acts as a competitive inhibitor at nicotinic acetylcholine receptors in the nervous system resulting in impairment of normal nerve function. Scientific literature on human imidacloprid po...

The single kinin receptor signals to separate and independent physiological pathways in Malpighian tubules of the yellow fever mosquito

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In the past we have used the leucokinins, the kinins of the cockroach Leucophaea, to evaluate the mechanism of diuretic action of kinin peptides in Malpighian tubules of the yellow fever mosquito Aedes aegypti. Now using aedeskinins, the kinins of Aedes, are available, we find that in isolated Aede...

Molecular analysis of the sea anemone toxin Av3 reveals selectivity to insects and demonstrates the heterogeneity of receptor site-3 on voltage-gated Na+ channels.

Science.gov (United States)

Moran, Yehu; Kahn, Roy; Cohen, Lior; Gur, Maya; Karbat, Izhar; Gordon, Dalia; Gurevitz, Michael

2007-08-15

Av3 is a short peptide toxin from the sea anemone Anemonia viridis shown to be active on crustaceans and inactive on mammals. It inhibits inactivation of Na(v)s (voltage-gated Na+ channels) like the structurally dissimilar scorpion alpha-toxins and type I sea anemone toxins that bind to receptor site-3. To examine the potency and mode of interaction of Av3 with insect Na(v)s, we established a system for its expression, mutagenized it throughout, and analysed it in toxicity, binding and electrophysiological assays. The recombinant Av3 was found to be highly toxic to blowfly larvae (ED50=2.65+/-0.46 pmol/100 mg), to compete well with the site-3 toxin LqhalphaIT (from the scorpion Leiurus quinquestriatus) on binding to cockroach neuronal membranes (K(i)=21.4+/-7.1 nM), and to inhibit the inactivation of Drosophila melanogaster channel, DmNa(v)1, but not that of mammalian Na(v)s expressed in Xenopus oocytes. Moreover, like other site-3 toxins, the activity of Av3 was synergically enhanced by ligands of receptor site-4 (e.g. scorpion beta-toxins). The bioactive surface of Av3 was found to consist mainly of aromatic residues and did not resemble any of the bioactive surfaces of other site-3 toxins. These analyses have portrayed a toxin that might interact with receptor site-3 in a different fashion compared with other ligands of this site. This assumption was corroborated by a D1701R mutation in DmNa(v)1, which has been shown to abolish the activity of all other site-3 ligands, except Av3. All in all, the present study provides further evidence for the heterogeneity of receptor site-3, and raises Av3 as a unique model for design of selective anti-insect compounds.

A proteomic approach for studying insect phylogeny: CAPA peptides of ancient insect taxa (Dictyoptera, Blattoptera as a test case

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Gäde Gerd

2009-03-01

Full Text Available Abstract Background Neuropeptide ligands have to fit exactly into their respective receptors and thus the evolution of the coding regions of their genes is constrained and may be strongly conserved. As such, they may be suitable for the reconstruction of phylogenetic relationships within higher taxa. CAPA peptides of major lineages of cockroaches (Blaberidae, Blattellidae, Blattidae, Polyphagidae, Cryptocercidae and of the termite Mastotermes darwiniensis were chosen to test the above hypothesis. The phylogenetic relationships within various groups of the taxon Dictyoptera (praying mantids, termites and cockroaches are still highly disputed. Results Tandem mass spectrometry of neuropeptides from perisympathetic organs was used to obtain sequence data of CAPA peptides from single specimens; the data were analysed by Maximum Parsimony and Bayesian Interference. The resulting cladograms, taking 61 species into account, show a topology which is in general agreement with recent molecular and morphological phylogenetic analyses, including the recent phylogenetic arrangement placing termites within the cockroaches. When sequence data sets from other neuropeptides, viz. adipokinetic hormones and sulfakinins, were included, the general topology of the cladogram did not change but bootstrap values increased considerably. Conclusion This study represents the first comprehensive survey of neuropeptides of insects for solely phylogenetic purposes and concludes that sequences of short neuropeptides are suitable to complement molecular biological and morphological data for the reconstruction of phylogenetic relationships.

An investigation into the chemical composition of alternative invertebrate prey

NARCIS (Netherlands)

Oonincx, D.G.A.B.; Dierenfeld, E.S.

2012-01-01

The aim of this study was to determine the chemical composition of eight invertebrate species and evaluate their suitability as alternative prey. The species selected were rusty red cockroaches (Blatta lateralis), six-spotted cockroaches (Eublaberus distanti), Madagascar hissing cockroaches

Subchronic exposure to sublethal dose of imidacloprid changes electrophysiological properties and expression pattern of nicotinic acetylcholine receptor subtypes in insect neurosecretory cells.

Science.gov (United States)

Benzidane, Yassine; Goven, Delphine; Abd-Ella, Aly Ahmed; Deshayes, Caroline; Lapied, Bruno; Raymond, Valérie

2017-09-01

Neonicotinoids are the most important class of insecticides used in agriculture over the last decade. They act as selective agonists of insect nicotinic acetylcholine receptors (nAChRs). The emergence of insect resistance to these insecticides is one of the major problems, which limit the use of neonicotinoids. The aim of our study is to better understand physiological changes appearing after subchronic exposure to sublethal doses of insecticide using complementary approaches that include toxicology, electrophysiology, molecular biology and calcium imaging. We used cockroach neurosecretory cells identified as dorsal unpaired median (DUM) neurons, known to express two α-bungarotoxin-insensitive (α-bgt-insensitive) nAChR subtypes, nAChR1 and nAChR2, which differ in their sensitivity to imidacloprid. Although nAChR1 is sensitive to imidacloprid, nAChR2 is insensitive to this insecticide. In this study, we demonstrate that subchronic exposure to sublethal dose of imidacloprid differentially changes physiological and molecular properties of nAChR1 and nAChR2. Our findings reported that this treatment decreased the sensitivity of nAChR1 to imidacloprid, reduced current density flowing through this nAChR subtype but did not affect its subunit composition (α3, α8 and β1). Subchronic exposure to sublethal dose of imidacloprid also affected nAChR2 functions. However, these effects were different from those reported on nAChR1. We observed changes in nAChR2 conformational state, which could be related to modification of the subunit composition (α1, α2 and β1). Finally, the subchronic exposure affecting both nAChR1 and nAChR2 seemed to be linked to the elevation of the steady-state resting intracellular calcium level. In conclusion, under subchronic exposure to sublethal dose of imidacloprid, cockroaches are capable of triggering adaptive mechanisms by reducing the participation of imidacloprid-sensitive nAChR1 and by optimizing functional properties of nAChR2, which is

Personality in the cockroach Diploptera punctata: Evidence for stability across developmental stages despite age effects on boldness.

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Stanley, Christina R; Mettke-Hofmann, Claudia; Preziosi, Richard F

2017-01-01

Despite a recent surge in the popularity of animal personality studies and their wide-ranging associations with various aspects of behavioural ecology, our understanding of the development of personality over ontogeny remains poorly understood. Stability over time is a central tenet of personality; ecological pressures experienced by an individual at different life stages may, however, vary considerably, which may have a significant effect on behavioural traits. Invertebrates often go through numerous discrete developmental stages and therefore provide a useful model for such research. Here we test for both differential consistency and age effects upon behavioural traits in the gregarious cockroach Diploptera punctata by testing the same behavioural traits in both juveniles and adults. In our sample, we find consistency in boldness, exploration and sociality within adults whilst only boldness was consistent in juveniles. Both boldness and exploration measures, representative of risk-taking behaviour, show significant consistency across discrete juvenile and adult stages. Age effects are, however, apparent in our data; juveniles are significantly bolder than adults, most likely due to differences in the ecological requirements of these life stages. Size also affects risk-taking behaviour since smaller adults are both bolder and more highly explorative. Whilst a behavioural syndrome linking boldness and exploration is evident in nymphs, this disappears by the adult stage, where links between other behavioural traits become apparent. Our results therefore indicate that differential consistency in personality can be maintained across life stages despite age effects on its magnitude, with links between some personality traits changing over ontogeny, demonstrating plasticity in behavioural syndromes.

Distribution of serotonergic and dopaminergic nerve fibers in the salivary gland complex of the cockroach Periplaneta americana

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Kühnel Dana

2002-06-01

Full Text Available Abstract Background The cockroach salivary gland consists of secretory acini with peripheral ion-transporting cells and central protein-producing cells, an extensive duct system, and a pair of reservoirs. Salivation is controled by serotonergic and dopaminergic innervation. Serotonin stimulates the secretion of a protein-rich saliva, dopamine causes the production of a saliva without proteins. These findings suggest a model in which serotonin acts on the central cells and possibly other cell types, and dopamine acts selectively on the ion-transporting cells. To examine this model, we have analyzed the spatial relationship of dopaminergic and serotonergic nerve fibers to the various cell types. Results The acinar tissue is entangled in a meshwork of serotonergic and dopaminergic varicose fibers. Dopaminergic fibers reside only at the surface of the acini next to the peripheral cells. Serotonergic fibers invade the acini and form a dense network between central cells. Salivary duct segments close to the acini are locally associated with dopaminergic and serotonergic fibers, whereas duct segments further downstream have only dopaminergic fibers on their surface and within the epithelium. In addition, the reservoirs have both a dopaminergic and a serotonergic innervation. Conclusion Our results suggest that dopamine is released on the acinar surface, close to peripheral cells, and along the entire duct system. Serotonin is probably released close to peripheral and central cells, and at initial segments of the duct system. Moreover, the presence of serotonergic and dopaminergic fiber terminals on the reservoir indicates that the functions of this structure are also regulated by dopamine and serotonin.

Personality in the cockroach Diploptera punctata: Evidence for stability across developmental stages despite age effects on boldness

Science.gov (United States)

Mettke-Hofmann, Claudia; Preziosi, Richard F.

2017-01-01

Despite a recent surge in the popularity of animal personality studies and their wide-ranging associations with various aspects of behavioural ecology, our understanding of the development of personality over ontogeny remains poorly understood. Stability over time is a central tenet of personality; ecological pressures experienced by an individual at different life stages may, however, vary considerably, which may have a significant effect on behavioural traits. Invertebrates often go through numerous discrete developmental stages and therefore provide a useful model for such research. Here we test for both differential consistency and age effects upon behavioural traits in the gregarious cockroach Diploptera punctata by testing the same behavioural traits in both juveniles and adults. In our sample, we find consistency in boldness, exploration and sociality within adults whilst only boldness was consistent in juveniles. Both boldness and exploration measures, representative of risk-taking behaviour, show significant consistency across discrete juvenile and adult stages. Age effects are, however, apparent in our data; juveniles are significantly bolder than adults, most likely due to differences in the ecological requirements of these life stages. Size also affects risk-taking behaviour since smaller adults are both bolder and more highly explorative. Whilst a behavioural syndrome linking boldness and exploration is evident in nymphs, this disappears by the adult stage, where links between other behavioural traits become apparent. Our results therefore indicate that differential consistency in personality can be maintained across life stages despite age effects on its magnitude, with links between some personality traits changing over ontogeny, demonstrating plasticity in behavioural syndromes. PMID:28489864

Mechanical properties of the cuticles of three cockroach species that differ in their wind-evoked escape behavior

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Andrew J. Clark

2014-07-01

Full Text Available The structural and material properties of insect cuticle remain largely unexplored, even though they comprise the majority (approximately 80% of animals. Insect cuticle serves many functions, including protection against predatory attacks, which is especially beneficial to species failing to employ effective running escape responses. Despite recent advances in our understanding of insect escape behaviors and the biomechanics of insect cuticle, there are limited studies on the protective qualities of cuticle to extreme mechanical stresses and strains imposed by predatory attacks, and how these qualities vary between species employing different escape responses. Blattarians (cockroaches provide an appropriate model system for such studies. Wind-evoked running escape responses are strong in Periplaneta americana, weak in Blaberus craniifer and absent in Gromphodorhina portentosa, putting the latter two species at greater risk of being struck by a predator. We hypothesized that the exoskeletons in these two larger species could provide more protection from predatory strikes relative to the exoskeleton of P. americana. We quantified the protective qualities of the exoskeletons by measuring the puncture resistance, tensile strength, strain energy storage, and peak strain in fresh samples of thoracic and abdominal cuticles from these three species. We found a continuum in puncture resistance, tensile strength, and strain energy storage between the three species, which were greatest in G. portentosa, moderate in B. craniifer, and smallest in P. americana. Histological measurements of total cuticle thickness followed this same pattern. However, peak strain followed a different trend between species. The comparisons in the material properties drawn between the cuticles of G. portentosa, B. craniifer, and P. americana demonstrate parallels between cuticular biomechanics and predator running escape responses.

Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism.

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Levy, Bruce D; Lukacs, Nicholas W; Berlin, Aaron A; Schmidt, Birgitta; Guilford, William J; Serhan, Charles N; Parkinson, John F

2007-12-01

Cellular recruitment during inflammatory/immune responses is tightly regulated. The ability to dampen inflammation is imperative for prevention of chronic immune responses, as in asthma. Here we investigated the ability of lipoxin A4 (LXA4) stable analogs to regulate airway responses in two allergen-driven models of inflammation. A 15-epi-LXA4 analog (ATLa) and a 3-oxa-15-epi-LXA4 analog (ZK-994) prevented excessive eosinophil and T lymphocyte accumulation and activation after mice were sensitized and aerosol-challenged with ovalbumin. At 50% and to a greater extent than equivalent doses of the CysLT1 receptor antagonist montelukast. Distinct from montelukast, ATLa treatment led to marked reductions in cysteinyl leukotrienes, interleukin-4 (IL-4), and IL-10, and both ATLa and ZK-994 inhibited levels of IL-13. In cockroach allergen-induced airway responses, both intraperitoneal and oral administration of ZK-994 significantly reduced parameters of airway inflammation and hyper-responsiveness in a dose-dependent manner. ZK-994 also significantly changed the balance of Th1/Th2-specific cytokine levels. Thus, the ATLa/LXA4 analog actions are distinct from CysLT1 antagonism and potently block both allergic airway inflammation and hyper-reactivity. Moreover, these results demonstrate these analogs' therapeutic potential as new agonists for the resolution of inflammation.

Adipokinetic hormones control amylase activity in the cockroach (Periplaneta americana) gut

Czech Academy of Sciences Publication Activity Database

Bodláková, K.; Jedlička, Pavel; Kodrík, Dalibor

2017-01-01

Roč. 24, č. 2 (2017), s. 259-269 ISSN 1672-9609 R&D Projects: GA ČR GA14-07172S Institutional support: RVO:61388963 ; RVO:60077344 Keywords : AKH * AKH receptor * amylase * enzyme * gene expression * midgut Subject RIV: ED - Physiology OBOR OECD: Entomology; Biochemistry and molecular biology (BC-A) Impact factor: 2.026, year: 2016

Receptor-receptor interactions within receptor mosaics. Impact on neuropsychopharmacology.

Science.gov (United States)

Fuxe, K; Marcellino, D; Rivera, A; Diaz-Cabiale, Z; Filip, M; Gago, B; Roberts, D C S; Langel, U; Genedani, S; Ferraro, L; de la Calle, A; Narvaez, J; Tanganelli, S; Woods, A; Agnati, L F

2008-08-01

Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson's disease, schizophrenia and drug addiction or drug dependence may substantially build on the existence of intramembrane receptor-receptor interactions within dopamine receptor containing receptor mosaics (RM; dimeric or high-order receptor oligomers) where it is believed that the dopamine D(2) receptor may operate as the 'hub receptor' within these complexes. The constitutive adenosine A(2A)/dopamine D(2) RM, located in the dorsal striato-pallidal GABA neurons, are of particular interest in view of the demonstrated antagonistic A(2A)/D(2) interaction within these heteromers; an interaction that led to the suggestion and later demonstration that A(2A) antagonists could be used as novel anti-Parkinsonian drugs. Based on the likely existence of A(2A)/D(2)/mGluR5 RM located both extrasynaptically on striato-pallidal GABA neurons and on cortico-striatal glutamate terminals, multiple receptor-receptor interactions within this RM involving synergism between A(2A)/mGluR5 to counteract D(2) signaling, has led to the proposal of using combined mGluR5 and A(2A) antagonists as a future anti-Parkinsonian treatment. Based on the same RM in the ventral striato-pallidal GABA pathways, novel strategies for the treatment of schizophrenia, building on the idea that A(2A) agonists and/or mGluR5 agonists will help reduce the increased dopaminergic signaling associated with this disease, have been suggested. Such treatment may ensure the proper glutamatergic drive from the mediodorsal thalamic nucleus to the prefrontal cortex, one which is believed to be reduced in schizophrenia due to a dominance of D(2)-like signaling in the ventral striatum. Recently, A(2A) receptors also have been shown to counteract the locomotor and sensitizing actions of cocaine and increases in A(2A) receptors have also been observed in the nucleus accumbens after extended cocaine self-administration, probably

Application of irradiation in bait production to the control of crawling insects in urban areas

Science.gov (United States)

Migdał, W.; Owczarczyk, H. B.; Świ ȩtosławski, J.; Świ ȩtosławski, J.

2000-03-01

The efficiency and palatability of two baits were studied to the control of crawling insects in urban areas: "Cockroach Kill Gel" for control of cockroaches and Faratox B for control of ants. Ionizing energy was used in producing the baits. It was concluded, that after irradiation the palatability of Faratox B improved and palatability of Cockroach Kill Gel did not change.

Application of irradiation in bait production to the control of crawling insects in urban areas

International Nuclear Information System (INIS)

Migdal, W.; Owczarczyk, H.B.; Swietoslawski, J.; Swietoslawski, J.

2000-01-01

The efficiency and palatability of two baits were studied to the control of crawling insects in urban areas: 'Cockroach Kill Gel' for control of cockroaches and Faratox B for control of ants. Ionizing energy was used in producing the baits. It was concluded, that after irradiation the palatability of Faratox B improved and palatability of Cockroach Kill Gel did not change

Application of irradiation in bait production to the control of crawling insects in urban areas

Energy Technology Data Exchange (ETDEWEB)

Migdal, W.; Owczarczyk, H.B.; Swietoslawski, J.; Swietoslawski, J

2000-03-01

The efficiency and palatability of two baits were studied to the control of crawling insects in urban areas: 'Cockroach Kill Gel' for control of cockroaches and Faratox B for control of ants. Ionizing energy was used in producing the baits. It was concluded, that after irradiation the palatability of Faratox B improved and palatability of Cockroach Kill Gel did not change.

Mars is close to venus--female reproductive proteins are expressed in the fat body and reproductive tract of honey bee (Apis mellifera L.) drones.

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Colonello-Frattini, Nínive Aguiar; Guidugli-Lazzarini, Karina Rosa; Simões, Zilá Luz Paulino; Hartfelder, Klaus

2010-11-01

Vitellogenin (Vg) and lipophorin (Lp) are lipoproteins which play important roles in female reproductive physiology of insects. Both are actively taken up by growing oocytes and especially Vg and its receptor are considered as female-specifically expressed. The finding that the fat body of in honey bee (Apis mellifera) drones synthesizes Vg and is present in hemolymph has long been viewed as a curiosity. The recent paradigm change concerning the role played by Vg in honey bee life history, especially social division of labor, has now led us to investigate whether a physiological constellation similar to that seen in female reproduction may also be represented in the male sex. By means of Western blot analysis we could show that both Vg and Lp are present in the reproductive tract of adult drones, including the accessory (mucus) glands, but apparently are not secreted. Furthermore, we analyzed the transcript levels of the genes encoding these proteins (vg and lp), as well as their putative receptors (Amvgr and Amlpr) in fat body and accessory glands. Whereas lp, vg and Amlpr transcript levels decreased with age in both tissues, Amvgr mRNA levels increased with age in fat body. To our knowledge this is the first report that vitellogenin and its receptor are co-expressed in the reproductive system of a male insect. We interpret these findings as a cross-sexual transfer of a social physiological trait, associated with the rewiring of the juvenile hormone/vitellogenin circuitry that occurred in the female sex of honey bees. Copyright 2010 Elsevier Ltd. All rights reserved.

Are eavesdroppers multimodal? Sensory exploitation of flo-ral signals by a non-native cockroach Blatta orientalis

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Rodrigo C. VERGARA, Alejandra TORRES-ARANEDA, Diego A. VILLAGRA, Robert A. RAGUSO, Mary T. K. ARROYO, Cristian A. VILLAGRA

2011-04-01

Full Text Available The study of multi-modal communication has only recently been extended to innate and learned interactions between flowers and their animal visitors, and usually only to pollinators. Here we studied the relevance of floral scent and visual display of a night blooming, putatively hawkmoth-pollinated plant Oenothera acaulis (Onagraceae in the attraction of non-native cockroaches Blatta orientalis (Blattodea: Blattidae, which function as facultative floral larcenists in coastal habitats of central Chile. We experimentally decoupled visual (corolla and olfactory (fragrance stimuli by presenting paper corollas and green mesh bags, with or without a freshly-picked natural flower inside. We then contrasted the behavioral responses of roaches in these treatments with those to the natural combination of traits in actual flowers and their respective control treatments, measuring the roaches’ frequency of first visits, mean and total residence time spent in each treatment. The roaches primarily used olfactory cues when approaching O. acaulis flowers at two biologically relevant spatial scales. In addition, the presence of conspecific roaches had a strong influence on recruitment to the experimental arena, increasing the statistical differences among treatments. Our results suggest a primacy of floral fragrance over visual stimuli in the foraging responses of B. orientalis. Olfactory cues were necessary and sufficient to attract the roaches, and the visual cues presented in our manipulations only marginally increased their attraction within a 20 cm diameter of the stimulus. The full spectrum of floral visitation behavior was not elicited by the artificial flowers, suggesting the need for additional tactile or contact chemosensory stimuli not provided by paper. Although the nitrogenous scent compounds that we found in O. acaulis flowers are almost exclusively found in hawkmoth-pollinated flowers, the attractiveness of these compounds to a non

Multifaceted defense against antagonistic microbes in developing offspring of the parasitoid wasp Ampulex compressa (Hymenoptera, Ampulicidae.

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Katharina Weiss

Full Text Available Effective antimicrobial strategies are essential adaptations of insects to protect themselves, their offspring, and their foods from microbial pathogens and decomposers. Larvae of the emerald cockroach wasp, Ampulex compressa, sanitize their cockroach hosts, Periplaneta americana, with a cocktail of nine antimicrobials comprising mainly (R-(--mellein and micromolide. The blend of these antimicrobials has broad-spectrum antimicrobial activity. Here we explore the spatio-temporal pattern of deployment of antimicrobials during the development from egg to adult as well as their physico-chemical properties to assess how these aspects may contribute to the success of the antimicrobial strategy. Using gas chromatography/mass spectrometry (GC/MS we show that larvae start sanitizing their food as soon as they have entered their host to feed on its tissue. Subsequently, they impregnate the cockroach carcass with antimicrobials to create a hygienic substrate for cocoon spinning inside the host. Finally, the antimicrobials are incorporated into the cocoon. The antimicrobial profiles on cockroach and wasp cocoon differed markedly. While micromolide persisted on the cockroaches until emergence of the wasps, solid-phase microextraction sampling and GC/MS analysis revealed that (R-(--mellein vaporized from the cockroaches and accumulated in the enclosed nest. In microbial challenge assays (R-(--mellein in the headspace of parasitized cockroaches inhibited growth of entomopathogenic and opportunistic microbes (Serratia marcescens, Aspergillus sydowii, Metarhizium brunneum. We conclude that, in addition to food sanitation, A. compressa larvae enclose themselves in two defensive walls by impregnating the cocoon and the cockroach cuticle with antimicrobials. On top of that, they use vaporous (R-(--mellein to sanitize the nest by fumigation. This multifaceted antimicrobial defense strategy involving the spatially and temporally coordinated deployment of several

The physiological role of fat body and muscle tissues in response to cold stress in the tropical cockroach Gromphadorhina coquereliana.

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Szymon Chowański

Full Text Available Protective mechanisms against cold stress are well studied in terrestrial and polar insects; however, little is known about these mechanisms in tropical insects. In our study, we tested if a tropical cockroach Gromphadorhina coquereliana, possesses any protective mechanisms against cold stress. Based on the results of earlier studies, we examined how short-term (3 h cold (4°C influences biochemical parameters, mitochondrial respiration activity, and the level of HSPs and aquaporins expression in the fat body and leg muscles of G. coquereliana. Following cold exposure, we found that the level of carbohydrates, lipids and proteins did not change significantly. Nevertheless, we observed significant changes in mitochondrial respiration activity. The oxygen consumption of resting (state 4 and phosphorylating (state 3 mitochondria was altered following cold exposure. The increase in respiratory rate in state 4 respiration was observed in both tissues. In state 3, oxygen consumption by mitochondria in fat body was significantly lower compared to control insects, whereas there were no changes observed for mitochondria in muscle tissue. Moreover, there were cold-induced changes in UCP protein activity, but the changes in activity differed in fat body and in muscles. Additionally, we detected changes in the level of HSP70 and aquaporins expression. Insects treated with cold had significantly higher levels of HSP70 in fat body and muscles. On the other hand, there were lower levels of aquaporins in both tissues following exposure to cold. These results suggest that fat body play an important role in protecting tropical insects from cold stress.

Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

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Luigi F. Agnati

2007-01-01

Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

Flight metabolism in Panstrongylus megistus (Hemiptera: Reduviidae): the role of carbohydrates and lipids

OpenAIRE

Canavoso, Lilián E; Stariolo, Raúl; Rubiolo, Edilberto R

2003-01-01

The metabolism of lipids and carbohydrates related to flight activity in Panstrongylus megistus was investigated. Insects were subjected to different times of flight under laboratory conditions and changes in total lipids, lipophorin density and carbohydrates were followed in the hemolymph. Lipids and glycogen were also assayed in fat body and flight muscle. In resting insects, hemolymph lipids averaged 3.4 mg/ml and significantly increased after 45 min of flight (8.8 mg/ml, P < 0.001). High-...

Somatostatin receptors

DEFF Research Database (Denmark)

Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

2003-01-01

functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

Insect-specific irreversible inhibitors of acetylcholinesterase in pests including the bed bug, the eastern yellowjacket, German and American cockroaches, and the confused flour beetle.

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Polsinelli, Gregory A; Singh, Sanjay K; Mishra, Rajesh K; Suranyi, Robert; Ragsdale, David W; Pang, Yuan-Ping; Brimijoin, Stephen

2010-09-06

Insecticides directed against acetylcholinesterase (AChE) are facing increased resistance among target species as well as increasing concerns for human toxicity. The result has been a resurgence of disease vectors, insects destructive to agriculture, and residential pests. We previously reported a free cysteine (Cys) residue at the entrance to the AChE active site in some insects but not higher vertebrates. We also reported Cys-targeting methanethiosulfonate molecules (AMTSn), which, under conditions that spared human AChE, caused total irreversible inhibition of aphid AChE, 95% inhibition of AChE from the malaria vector mosquito (Anopheles gambia), and >80% inhibition of activity from the yellow fever mosquito (Aedes aegypti) and northern house mosquito (Culex pipiens). We now find the same compounds inhibit AChE from cockroaches (Blattella germanica and Periplaneta americana), the flour beetle (Tribolium confusum), the multi-colored Asian ladybird beetle (Harmonia axyridis), the bed bug (Cimex lectularius), and a wasp (Vespula maculifrons), with IC(50) values of approximately 1-11muM. Our results support further study of Cys-targeting inhibitors as conceptually novel insecticides that may be free of resistance in a range of insect pests and disease vectors and, compared with current compounds, should demonstrate much lower toxicity to mammals, birds, and fish. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Accurate quantification of 5 German cockroach (GCr) allergens in complex extracts using multiple reaction monitoring mass spectrometry (MRM MS).

Science.gov (United States)

Mindaye, S T; Spiric, J; David, N A; Rabin, R L; Slater, J E

2017-12-01

German cockroach (GCr) allergen extracts are complex and heterogeneous products, and methods to better assess their potency and composition are needed for adequate studies of their safety and efficacy. The objective of this study was to develop an assay based on liquid chromatography and multiple reaction monitoring mass spectrometry (LC-MRM MS) for rapid, accurate, and reproducible quantification of 5 allergens (Bla g 1, Bla g 2, Bla g 3, Bla g 4, and Bla g 5) in crude GCr allergen extracts. We first established a comprehensive peptide library of allergens from various commercial extracts as well as recombinant allergens. Peptide mapping was performed using high-resolution MS, and the peptide library was then used to identify prototypic and quantotypic peptides to proceed with MRM method development. Assay development included a systematic optimization of digestion conditions (buffer, digestion time, and trypsin concentration), chromatographic separation, and MS parameters. Robustness and suitability were assessed following ICH (Q2 [R1]) guidelines. The method is precise (RSD  0.99, 0.01-1384 fmol/μL), and sensitive (LLOD and LLOQ MS, we quantified allergens from various commercial GCr extracts and showed considerable variability that may impact clinical efficacy. Our data demonstrate that the LC-MRM MS method is valuable for absolute quantification of allergens in GCr extracts and likely has broader applicability to other complex allergen extracts. Definitive quantification provides a new standard for labelling of allergen extracts, which will inform patient care, enable personalized therapy, and enhance the efficacy of immunotherapy for environmental and food allergies. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Insulin receptors

International Nuclear Information System (INIS)

Kahn, C.R.; Harrison, L.C.

1988-01-01

This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

Pathogenic Fungal Species Associated with Digestive System of Periplaneta americana (Blattaria: Blattidae Trapped from Residential Dwellings in Ahvaz City, Southwestern Iran

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Hamid Kassiri

2018-03-01

Full Text Available Background: Cockroaches are the most prevalent domestic pests of a worldwide distribution. They were recognized as possible vectors of pathogenic bacteria, viruses, fungi and parasites in residential dwellings and hospital environ­ments. The present study isolated and identified yeasts and filamentous fungi from digestive tract of American cock­roaches, collected from three different residential regions of Iran.Methods: Seventy cockroaches were sampled using direct collection (hand catch, vacuum cleaner and sticky traps in Ahvaz, Iran in 2009–2010. Their medically important fungal microorganisms were isolated from digestive tract using standard mycological methods. Filamentous fungi were identified by macroscopic and microscopic examina­tion. Yeasts were identified by API ID32C-32100 kit.Results: A high percentage of cockroaches (88.6% were detected to carry fungi of medical importance. Overall, 23 fungi species/genera were isolated from the American cockroaches' alimentary tract. The fungi isolated from cock­roaches, from the residential regions were species of Aspergillus, Rhizopus, Penicillium, Mucorales, Alternaria, Cladosporium, Mycelia, Chrysosporium, Candida, Rhodotorula, Zygosaccharomyces, and Debaryomyces. Candida spp. (41.4%, Aspergillus spp. (37.1% and Rhodotorula spp (27.1% were the most common fungi recovered on cockroaches. Candida albicans and Candida glabrata were the commonest species of the genus Candida. In addi­tion, Aspergillus niger and A. flavus were the most frequent species of the genus Aspergillus.Conclusion: American cockroaches may carry pathogenic fungi in the urban areas of Ahvaz.

Phytochemical Composition And Effect Of Aqueous Extract Of ...

African Journals Online (AJOL)

Phytochemical Composition And Effect Of Aqueous Extract Of Struchium sparganophora (L) On Cockroach Crude Extract – Induced Airway Inflammatory ... Similarly, mean percentages of neutrophils, lymphyocytes, and eosinophils in cockroach crude extract-induced rats administered with S. sparganophora crude extract ...

Prevalence and Antibiotic Resistance of Gram-Negative Pathogenic Bacteria Species Isolated from Periplaneta americana and Blattella germanica in Varanasi, India.

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D Leshan Wannigama

2014-06-01

Full Text Available Cockroaches are among the medically important pests found within the human habitations that cause serious public health problems. They may harbor a number of pathogenic bacteria on the external surface with antibiotic resistance. Hence, they are regarded as major microbial vectors. This study investigates the prevalence and antibiotic resistance of Gram-negative pathogenic bacteria species isolated from Periplaneta americana and Blattella germanica in Varanasi, India.Totally, 203 adult cockroaches were collected form 44 households and 52 food-handling establishments by trapping. Bacteriological examination of external surfaces of Pe. americana and Bl. germanica were carried out using standard method and antibiotics susceptibility profiles of the isolates were determined using Kirby-Bauer disc diffusion methods.Among the places, we found that 54% had cockroache infestation in households and 77% in food- handling establishments. There was no significant different between the overall bacteria load of the external surface in Pe. americana (64.04% and Bl. germanica (35.96%. However the predominant bacteria on cockroaches were Klebsiella pneumonia, Escherichia coli, Enterobacter aerogenes, and Pseudomonas aeruginosa. However, Kl. pneumoniae and Ps. aeruginosa were the most prevalent, drug-resistant strains were isolated from the cockroaches with 100% resistance to sulfamethoxazole/trimethoprim and ampicillin. For individual strains of bacteria, Escherichia coli was found to have multi-resistance to four antibiotic tested, Citrobacter freundii four, Enterobacter aerogenes and Proteus mirabilis to three.Cockroaches are uniformly distributed in domestic environment, which can be a possible vector for transmission of drug-resistant bacteria and food-borne diseases.

The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

Science.gov (United States)

Keegan, A D; Pierce, J H

1994-02-01

Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

The LDL receptor.

Science.gov (United States)

Goldstein, Joseph L; Brown, Michael S

2009-04-01

In this article, the history of the LDL receptor is recounted by its codiscoverers. Their early work on the LDL receptor explained a genetic cause of heart attacks and led to new ways of thinking about cholesterol metabolism. The LDL receptor discovery also introduced three general concepts to cell biology: receptor-mediated endocytosis, receptor recycling, and feedback regulation of receptors. The latter concept provides the mechanism by which statins selectively lower plasma LDL, reducing heart attacks and prolonging life.

Vasoconstrictive effect of Xinmailong injection in rat aorta | Yang ...

African Journals Online (AJOL)

Background: Cockroach has been traditionally utilized in China for the therapy of cardiovascular disorders, such as heart failure. The present study was aimed to assess the vasoconstrictive effect of Xinmailong Injection (XML), a bioactive composite from American cockroach. Methodology: The isometric tensions of rat aortic ...

Potential costs of bacterial infection on storage protein gene expression and reproduction in queenless Apis mellifera worker bees on distinct dietary regimes.

Science.gov (United States)

Lourenço, Anete Pedro; Martins, Juliana Ramos; Guidugli-Lazzarini, Karina Rosa; Macedo, Liliane Maria Fróes; Bitondi, Márcia Maria Gentile; Simões, Zilá Luz Paulino

2012-09-01

Insects are able to combat infection by initiating an efficient immune response that involves synthesizing antimicrobial peptides and a range of other defense molecules. These responses may be costly to the organism, resulting in it exploiting endogenous resources to maintain homeostasis or support defense to the detriment of other physiological needs. We used queenless worker bees on distinct dietary regimes that may alter hemolymph protein storage and ovary activation to investigate the physiological costs of infection with Serratia marcescens. The expression of the genes encoding the storage proteins vitellogenin and hexamerin 70a, the vitellogenin receptor, and vasa (which has a putative role in reproduction), was impaired in the infected bees. This impairment was mainly evident in the bees fed beebread, which caused significantly higher expression of these genes than did royal jelly or syrup, and this was confirmed at the vitellogenin and hexamerin 70a protein levels. Beebread was also the only diet that promoted ovary activation in the queenless bees, but this activation was significantly impaired by the infection. The expression of the genes encoding the storage proteins apolipophorins-I and -III and the lipophorin receptor was not altered by infection regardless the diet provided to the bees. Similarly, the storage of apolipophorin-I in the hemolymph was only slightly impaired by the infection, independently of the supplied diet. Taken together these results indicate that, infection demands a physiological cost from the transcription of specific protein storage-related genes and from the reproductive capacity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Specific B-cell Epitope of Per a 1: A Major Allergen of American Cockroach (Periplaneta americana) and Anatomical Localization.

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Sookrung, Nitat; Khetsuphan, Thanyathon; Chaisri, Urai; Indrawattana, Nitaya; Reamtong, Onrapak; Chaicumpa, Wanpen; Tungtrongchitr, Anchalee

2014-07-01

Cockroach (CR) is a common source of indoor allergens, and Per a 1 is a major American CR (Periplaneta americana) allergen; however, several attributes of this protein remain unknown. This study identifies a novel specific B cell epitope and anatomical locations of Per a 1.0105. Recombinant Per a 1.0105 (rPer a 1.0105) was used as BALB/c mouse immunogen for the production of monoclonal antibodies (MAb). The MAb specific B cell epitope was identified by determining phage mimotopic peptides and pair-wise alignment of the peptides with the rPer a 1.0105 amino acid sequence. Locations of the Per a 1.0105 in P. americana were investigated by immunohistochemical staining. The rPer a 1.0105 (~13 kDa) had 100%, 98% and ≥90% identity to Per a 1.0105, Per a 1.0101, and Cr-PII, respectively. The B-cell epitope of the Per a 1.0105 specific-MAb was located at residues(99) QDLLLQLRDKGV(110) contained in all 5 Per a 1.01 isoforms and Per a 1.02. The epitope was analogous to the Bla g 1.02 epitope; however, this B-cell epitope was not an IgE inducer. Per a 1.0105 was found in the midgut and intestinal content of American CR but not in the other organs. The amount of the Per a 1 was ~544 ℃g per gram of feces. The novel Per a 1 B-cell epitope described in this study is a useful target for allergen quantification in samples; however, the specific MAb can be used as an allergen detection reagent. The MAb based-affinity resin can be made for allergen purification, and the so-purified protein can serve as a standard and diagnostic allergen as well as a therapeutic vaccine component. The finding that the Per a 1 is contained in the midgut and feces is useful to increase yield and purity when preparing this allergen.

Molecular cloning, expression, IgE binding activities and in silico epitope prediction of Per a 9 allergens of the American cockroach

Science.gov (United States)

Yang, Haiwei; Chen, Hao; Jin, Min; Xie, Hua; He, Shaoheng; Wei, Ji-Fu

2016-01-01

Per a 9 is a major allergen of the American cockroach (CR), which has been recognized as an important cause of imunoglobulin E-mediated type I hypersensitivity worldwide. However, it is not neasy to obtain a substantial quantity of this allergen for use in functional studies. In the present study, the Per a 9 gene was cloned and expressed in Escherichia coli (E. coli) systems. It was found that 13/16 (81.3%) of the sera from patients with allergies caused by the American CR reacted to Per a 9, as assessed by enzyme-linked immunosorbent assay, confirming that Per a 9 is a major allergen of CR. The induction of the expression of CD63 and CCR3 in passively sensitized basophils (from sera of patients with allergies caused by the American CR) by approximately 4.2-fold indicated that recombinant Per a 9 was functionally active. Three immunoinformatics tools, including the DNASTAR Protean system, Bioinformatics Predicted Antigenic Peptides (BPAP) system and the BepiPred 1.0 server were used to predict the potential B cell epitopes, while Net-MHCIIpan-2.0 and NetMHCII-2.2 were used to predict the T cell epitopes of Per a 9. As a result, we predicted 11 peptides (23–28, 39–46, 58–64, 91–118, 131–136, 145–154, 159–165, 176–183, 290–299, 309–320 and 338–344) as potential B cell linear epitopes. In T cell prediction, the Per a 9 allergen was predicted to have 5 potential T cell epitope sequences, 119–127, 194–202, 210–218, 239–250 and 279–290. The findings of our study may prove to be useful in the development of peptide-based vaccines to combat CR-induced allergies. PMID:27840974

β-Adrenergic receptor-mediated suppression of interleukin 2 receptors in human lymphocytes

International Nuclear Information System (INIS)

Feldman, R.D.; Hunninghake, G.W.; McArdle, W.L.

1987-01-01

Adrenergic receptor agonists are know to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of β-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the β-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL-2 receptor anti-TAC antibody. To determine the effect of β-adrenergic agonists on expression of the high affinity IL-2 receptors, [ 125 I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of β-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that β-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites

1912-IJBCS-Article-Brown Charles

African Journals Online (AJOL)

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MATERIALS AND METHODS. Sampling sites and sample collection. Cockroaches were collected, from the main kitchen of the hospital and the balconies of the hostel rooms from May-June, 2011, using sugar-baited traps placed overnight at suitable positions at the sampling sites. Each trapped cockroach was transferred, ...

Quantitative receptor radioautography in the study of receptor-receptor interactions in the nucleus tractus solitarii

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Fior-Chadi D.R.

1998-01-01

Full Text Available The nucleus tractus solitarii (NTS in the dorsomedial medulla comprises a wide range of neuropeptides and biogenic amines. Several of them are related to mechanisms of central blood pressure control. Angiotensin II (Ang II, neuropeptide Y (NPY and noradrenaline (NA are found in the NTS cells, as well as their receptors. Based on this observation we have evaluated the modulatory effect of these peptide receptors on a2-adrenoceptors in the NTS. Using quantitative receptor radioautography, we observed that NPY and Ang II receptors decreased the affinity of a2-adrenoceptors for their agonists in the NTS of the rat. Cardiovascular experiments agreed with the in vitro data. Coinjection of a threshold dose of Ang II or of the NPY agonists together with an ED50 dose of adrenergic agonists such as NA, adrenaline and clonidine counteracted the depressor effect produced by the a2-agonist in the NTS. The results provide evidence for the existence of an antagonistic interaction between Ang II at1 receptors and NPY receptor subtypes with the a2-adrenoceptors in the NTS. This receptor interaction may reduce the transduction over the a2-adrenoceptors which can be important in central cardiovascular regulation and in the development of hypertension

XMRV: usage of receptors and potential co-receptors

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Gaddam Durga

2011-09-01

Full Text Available Abstract Background XMRV is a gammaretrovirus first identified in prostate tissues of Prostate Cancer (PC patients and later in the blood cells of patients with Chronic Fatigue Syndrome (CFS. Although XMRV is thought to use XPR1 for cell entry, it infects A549 cells that do not express XPR1, suggesting usage of other receptors or co-receptors. Methods To study the usage of different receptors and co- receptors that could play a role in XMRV infection of lymphoid cells and GHOST (GFP- Human osteosarcoma cells expressing CD4 along with different chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture supernatants and cells were tested for XMRV replication using real time quantitative PCR. Results Infection and replication of XMRV was seen in a variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of XMRV replication varied in different cell lines showing differential replication in different cell lines. However, replication in A549 which lacks XPR1 expression was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied in GHOST cell lines expressing CD4 and each of the co- receptors CCR1-CCR8 and bob. There was significant replication of XMRV in CCR3 and Bonzo although it is much lower when compared to DU145, A549 and LNCaP. Conclusion XMRV replication was observed in GHOST cells that express CD4 and each of the chemokine receptors ranging from CCR1- CCR8 and BOB suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors.

GABA receptor imaging

Energy Technology Data Exchange (ETDEWEB)

Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

2007-04-15

GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

GABA receptor imaging

International Nuclear Information System (INIS)

Lee, Jong Doo

2007-01-01

GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA A -receptor that allows chloride to pass through a ligand gated ion channel and GABA B -receptor that uses G-proteins for signaling. The GABA A -receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA A -receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with 11 C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, 18 F-fluoroflumazenil (FFMZ) has been developed to overcome 11 C's short half-life. 18 F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1 1 C-FMZ PET instead of 18 F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA A receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas

The two-state dimer receptor model: a general model for receptor dimers.

Science.gov (United States)

Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferrada, Carla; Ferré, Sergi; Fuxe, Kjell; Cortés, Antoni; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

2006-06-01

Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the "two-state dimer receptor model" has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the "two-independent-site receptor model", the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots.

Receptor oligomerization in family B1 of G-protein-coupled receptors

DEFF Research Database (Denmark)

Roed, Sarah Norklit; Ørgaard, Anne; Jørgensen, Rasmus

2012-01-01

, the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this......, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality......The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades...

Activation of glucocorticoid receptors increases 5-HT2A receptor levels

DEFF Research Database (Denmark)

Trajkovska, Viktorija; Kirkegaard, Lisbeth; Krey, Gesa

2009-01-01

an effect of GR activation on 5-HT2A levels, mature organotypic hippocampal cultures were exposed to corticosterone with or without GR antagonist mifepristone and mineralocorticoid receptor (MR) antagonist spironolactone. In GR under-expressing mice, hippocampal 5-HT2A receptor protein levels were decreased......Major depression is associated with both dysregulation of the hypothalamic pituitary adrenal axis and serotonergic deficiency, not the least of the 5-HT2A receptor. However, how these phenomena are linked to each other, and whether a low 5-HT2A receptor level is a state or a trait marker...... of depression is unknown. In mice with altered glucocorticoid receptor (GR) expression we investigated 5-HT2A receptor levels by Western blot and 3H-MDL100907 receptor binding. Serotonin fibre density was analyzed by stereological quantification of serotonin transporter immunopositive fibers. To establish...

Adhesion and friction of the smooth attachment system of the cockroach Gromphadorhina portentosa and the influence of the application of fluid adhesives

Directory of Open Access Journals (Sweden)

Oliver Betz

2017-05-01

Full Text Available Two different measurement techniques were applied to study the attachment of the smooth foot pads of the Madagascar hissing cockroach Gromphadorhina portentosa. The attachment of the non-manipulated adhesive organs was compared with that of manipulated ones (depletion or substitution by artificial secretions. From measurements of the friction on a centrifuge, it can be concluded that on nanorough surfaces, the insect appears to benefit from employing emulsions instead of pure oils to avoid excessive friction. Measurements performed with a nanotribometer on single attachment organs showed that, in the non-manipulated euplantulae, friction was clearly increased in the push direction, whereas the arolium of the fore tarsus showed higher friction in the pull direction. The surface of the euplantulae shows an imbricate appearance, whereupon the ledges face distally, which might contribute to the observed frictional anisotropy in the push direction. Upon depletion of the tarsal adhesion-mediating secretion or its replacement by oily fluids, in several cases, the anisotropic effect of the euplantula disappeared due to the decrease of friction forces in push-direction. In the euplantulae, adhesion was one to two orders of magnitude lower than friction. Whereas the tenacity was slightly decreased with depleted secretion, it was considerably increased after artificial application of oily liquids. In terms of adhesion, it is concluded that the semi-solid consistence of the natural adhesion-mediating secretion facilitates the detachment of the tarsus during locomotion. In terms of friction, on smooth to nanorough surfaces, the insects appear to benefit from employing emulsions instead of pure oils to avoid excessive friction forces, whereas on rougher surfaces the tarsal fluid rather functions in improving surface contact by keeping the cuticle compliable and compensating surface asperities of the substratum.

DC type 2 polarization depends on both the allergic status of the individual and protease activity of Per a 10.

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Goel, Chhavi; Gaur, S N; Bhati, Gaurav; Arora, Naveen

2015-10-01

Cockroach proteases are important risk factors for asthma development in predisposed individuals. In the present study, effect of allergic status of patients on DCs polarization in response to protease allergen Per a 10 was investigated. Cockroach-allergic, other-allergic patients and healthy individuals were selected following the guidelines of ATS/ARIA. Monocyte-derived dendritic cells (DCs) were generated from the selected individuals and stimulated with Per a 10. Flow cytometric analysis showed a significantly high expression of CD80 and CD86 on DCs from cockroach-allergic patients after Per a 10 stimulation as compared to healthy individuals or other-allergic patients (PPer a 10 induced comparable level of CD83 expression on DCs from all the 3 groups, showing it was irrespective of the allergic status. CD40 expression was significantly low (PPer a 10 induced lower CD40 expression on DCs than the heat-inactivated Per a 10 (PPer a 10 stimulated DC cultures was significantly higher than in heat-inactivated Per a 10 (PPer a 10-stimulated DCs than heat-inactivated Per a 10-stimulated DCs. Per a 10-stimulated DCs from cockroach-allergic patients secreted high levels of IL-5, IL-6, TNF-α than that from healthy individuals or other-allergic patients (PPer a 10-stimulated DCs from cockroach-allergic patients induced increased secretions of IL-4, IL-5, IL-6, TNF-α and low IL-12 by T cells as compared to those from other groups (PPer a 10 allergen, polarization of DCs shifts toward type 2 in cockroach-allergic patients but not in the healthy individuals or other-allergic patients. In conclusion, both allergic status of the individual and protease activity of Per a 10 are important parameters that participate in DCs polarization. Copyright © 2015 Elsevier GmbH. All rights reserved.

Gβ promotes pheromone receptor polarization and yeast chemotropism by inhibiting receptor phosphorylation.

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Ismael, Amber; Tian, Wei; Waszczak, Nicholas; Wang, Xin; Cao, Youfang; Suchkov, Dmitry; Bar, Eli; Metodiev, Metodi V; Liang, Jie; Arkowitz, Robert A; Stone, David E

2016-04-12

Gradient-directed cell migration (chemotaxis) and growth (chemotropism) are processes that are essential to the development and life cycles of all species. Cells use surface receptors to sense the shallow chemical gradients that elicit chemotaxis and chemotropism. Slight asymmetries in receptor activation are amplified by downstream signaling systems, which ultimately induce dynamic reorganization of the cytoskeleton. During the mating response of budding yeast, a model chemotropic system, the pheromone receptors on the plasma membrane polarize to the side of the cell closest to the stimulus. Although receptor polarization occurs before and independently of actin cable-dependent delivery of vesicles to the plasma membrane (directed secretion), it requires receptor internalization. Phosphorylation of pheromone receptors by yeast casein kinase 1 or 2 (Yck1/2) stimulates their internalization. We showed that the pheromone-responsive Gβγ dimer promotes the polarization of the pheromone receptor by interacting with Yck1/2 and locally inhibiting receptor phosphorylation. We also found that receptor phosphorylation is essential for chemotropism, independently of its role in inducing receptor internalization. A mathematical model supports the idea that the interaction between Gβγ and Yck1/2 results in differential phosphorylation and internalization of the pheromone receptor and accounts for its polarization before the initiation of directed secretion. Copyright © 2016, American Association for the Advancement of Science.

Glucocorticoid receptor modulators.

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Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

2018-06-01

The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Angiotensin type 2 receptor (AT2R) and receptor Mas

DEFF Research Database (Denmark)

Villela, Daniel; Leonhardt, Julia; Patel, Neal

2015-01-01

The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striki...

A search for presynaptic inhibitory histamine receptors in guinea-pig tissues: Further H3 receptors but no evidence for H4 receptors.

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Petri, Doris; Schlicker, Eberhard

2016-07-01

The histamine H4 receptor is coupled to Gi/o proteins and expressed on inflammatory cells and lymphoid tissues; it was suggested that this receptor also occurs in the brain or on peripheral neurones. Since many Gi/o protein-coupled receptors, including the H3 receptor, serve as presynaptic inhibitory receptors, we studied whether the sympathetic neurones supplying four peripheral tissues and the cholinergic neurones in the hippocampus from the guinea-pig are equipped with release-modulating H4 and H3 receptors. For this purpose, we preincubated tissue pieces from the aorta, atrium, renal cortex and vas deferens with (3)H-noradrenaline and hippocampal slices with (3)H-choline and determined the electrically evoked tritium overflow. The stimulation-evoked overflow in the five superfused tissues was inhibited by the muscarinic receptor agonist oxotremorine, which served as a positive control, but not affected by the H4 receptor agonist 4-methylhistamine. The H3 receptor agonist R-α-methylhistamine inhibited noradrenaline release in the peripheral tissues without affecting acetylcholine release in the hippocampal slices. Thioperamide shifted the concentration-response curve of histamine in the aorta and the renal cortex to the right, yielding apparent pA2 values of 8.0 and 8.1, respectively, which are close to its affinity at other H3 receptors but higher by one log unit than its pKi at the H4 receptor of the guinea-pig. In conclusion, histamine H4 receptors could not be identified in five experimental models of the guinea-pig that are suited for the detection of presynaptic inhibitory receptors whereas H3 receptors could be shown in the peripheral tissues but not in the hippocampus. This article is part of the Special Issue entitled 'Histamine Receptors'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transforming insect electromyograms into pneumatic muscle control

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Rutter, Brandon; Mu, Laiyong; Ritzmann, Roy; Quinn, Roger

2006-05-01

Robots can serve as hardware models for testing biological hypotheses. Both for this reason and to improve the state of the art of robotics, we strive to incorporate biological principles of insect locomotion into robotic designs. Previous research has resulted in a line of robots with leg designs based on walking and climbing movements of the cockroach Blaberus discoidalis. The current version, Robot V, uses muscle-like Braided Pneumatic Actuators (BPAs). In this paper, we use recorded electromyograms (EMGs) to drive robot joint motion. A muscle activation model was developed that transforms EMGs recorded from behaving cockroaches into appropriate commands for the robot. The transform is implemented by multiplying the EMG by an input gain thus generating an input pressure signal, which is used to drive a one-way closed loop pressure controller. The actuator then can be modeled as a capacitance with input rectification. The actuator exhaust valve is given a leak rate, making the transform a leaky integrator for air pressure, which drives the output force of the actuator. We find parameters of this transform by minimizing the difference between the robot motion produced and that observed in the cockroach. Although we have not reproduced full-amplitude cockroach motion using this robot, results from evaluation on reduced-amplitude cockroach angle data strongly suggest that braided pneumatic actuators can be used as part of a physical model of a biological system.

Real-Time G-Protein-Coupled Receptor Imaging to Understand and Quantify Receptor Dynamics

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María S. Aymerich

2011-01-01

Full Text Available Understanding the trafficking of G-protein-coupled receptors (GPCRs and their regulation by agonists and antagonists is fundamental to develop more effective drugs. Optical methods using fluorescent-tagged receptors and spinning disk confocal microscopy are useful tools to investigate membrane receptor dynamics in living cells. The aim of this study was to develop a method to characterize receptor dynamics using this system which offers the advantage of very fast image acquisition with minimal cell perturbation. However, in short-term assays photobleaching was still a problem. Thus, we developed a procedure to perform a photobleaching-corrected image analysis. A study of short-term dynamics of the long isoform of the dopamine type 2 receptor revealed an agonist-induced increase in the mobile fraction of receptors with a rate of movement of 0.08 μm/s For long-term assays, the ratio between the relative fluorescence intensity at the cell surface versus that in the intracellular compartment indicated that receptor internalization only occurred in cells co-expressing G protein-coupled receptor kinase 2. These results indicate that the lateral movement of receptors and receptor internalization are not directly coupled. Thus, we believe that live imaging of GPCRs using spinning disk confocal image analysis constitutes a powerful tool to study of receptor dynamics.

Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional Localization.

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Ozawa, Akihiko; Brunori, Gloria; Mercatelli, Daniela; Wu, Jinhua; Cippitelli, Andrea; Zou, Bende; Xie, Xinmin Simon; Williams, Melissa; Zaveri, Nurulain T; Low, Sarah; Scherrer, Grégory; Kieffer, Brigitte L; Toll, Lawrence

2015-08-19

The nociceptin/orphanin FQ (NOP) receptor, the fourth member of the opioid receptor family, is involved in many processes common to the opioid receptors including pain and drug abuse. To better characterize receptor location and trafficking, knock-in mice were created by inserting the gene encoding enhanced green fluorescent protein (eGFP) into the NOP receptor gene (Oprl1) and producing mice expressing a functional NOP-eGFP C-terminal fusion in place of the native NOP receptor. The NOP-eGFP receptor was present in brain of homozygous knock-in animals in concentrations somewhat higher than in wild-type mice and was functional when tested for stimulation of [(35)S]GTPγS binding in vitro and in patch-clamp electrophysiology in dorsal root ganglia (DRG) neurons and hippocampal slices. Inhibition of morphine analgesia was equivalent when tested in knock-in and wild-type mice. Imaging revealed detailed neuroanatomy in brain, spinal cord, and DRG and was generally consistent with in vitro autoradiographic imaging of receptor location. Multicolor immunohistochemistry identified cells coexpressing various spinal cord and DRG cellular markers, as well as coexpression with μ-opioid receptors in DRG and brain regions. Both in tissue slices and primary cultures, the NOP-eGFP receptors appear throughout the cell body and in processes. These knock-in mice have NOP receptors that function both in vitro and in vivo and appear to be an exceptional tool to study receptor neuroanatomy and correlate with NOP receptor function. The NOP receptor, the fourth member of the opioid receptor family, is involved in pain, drug abuse, and a number of other CNS processes. The regional and cellular distribution has been difficult to determine due to lack of validated antibodies for immunohistochemical analysis. To provide a new tool for the investigation of receptor localization, we have produced knock-in mice with a fluorescent-tagged NOP receptor in place of the native NOP receptor. These

Receptor assay

Energy Technology Data Exchange (ETDEWEB)

Kato, K; Ibayashi, H [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1975-05-01

This paper summarized present status and problems of analysis of hormone receptor and a few considerations on clinical significance of receptor abnormalities. It was pointed that in future clinical field quantitative and qualitative analysis of receptor did not remain only in the etiological discussion, but that it was an epoch-making field of investigation which contained the possiblity of artificial change of sensitivity of living body on drugs and the development connected directly with treatment of various diseases.

Calcitonin and calcitonin receptor-like receptors: common themes with family B GPCRs?

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Barwell, James; Gingell, Joseph J; Watkins, Harriet A; Archbold, Julia K; Poyner, David R; Hay, Debbie L

2012-05-01

The calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR) are two of the 15 human family B (or Secretin-like) GPCRs. CTR and CLR are of considerable biological interest as their pharmacology is moulded by interactions with receptor activity-modifying proteins. They also have therapeutic relevance for many conditions, such as osteoporosis, diabetes, obesity, lymphatic insufficiency, migraine and cardiovascular disease. In light of recent advances in understanding ligand docking and receptor activation in both the family as a whole and in CLR and CTR specifically, this review reflects how applicable general family B GPCR themes are to these two idiosyncratic receptors. We review the main functional domains of the receptors; the N-terminal extracellular domain, the juxtamembrane domain and ligand interface, the transmembrane domain and the intracellular C-terminal domain. Structural and functional findings from the CLR and CTR along with other family B GPCRs are critically appraised to gain insight into how these domains may function. The ability for CTR and CLR to interact with receptor activity-modifying proteins adds another level of sophistication to these receptor systems but means careful consideration is needed when trying to apply generic GPCR principles. This review encapsulates current thinking in the realm of family B GPCR research by highlighting both conflicting and recurring themes and how such findings relate to two unusual but important receptors, CTR and CLR. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

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Singer, M S; Shepherd, G M

1994-06-02

Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

Receptor downregulation and desensitization enhance the information processing ability of signalling receptors

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Resat Haluk

2007-11-01

Full Text Available Abstract Background In addition to initiating signaling events, the activation of cell surface receptors also triggers regulatory processes that restrict the duration of signaling. Acute attenuation of signaling can be accomplished either via ligand-induced internalization of receptors (endocytic downregulation or via ligand-induced receptor desensitization. These phenomena have traditionally been viewed in the context of adaptation wherein the receptor system enters a refractory state in the presence of sustained ligand stimuli and thereby prevents the cell from over-responding to the ligand. Here we use the epidermal growth factor receptor (EGFR and G-protein coupled receptors (GPCR as model systems to respectively examine the effects of downregulation and desensitization on the ability of signaling receptors to decode time-varying ligand stimuli. Results Using a mathematical model, we show that downregulation and desensitization mechanisms can lead to tight and efficient input-output coupling thereby ensuring synchronous processing of ligand inputs. Frequency response analysis indicates that upstream elements of the EGFR and GPCR networks behave like low-pass filters with the system being able to faithfully transduce inputs below a critical frequency. Receptor downregulation and desensitization increase the filter bandwidth thereby enabling the receptor systems to decode inputs in a wider frequency range. Further, system-theoretic analysis reveals that the receptor systems are analogous to classical mechanical over-damped systems. This analogy enables us to metaphorically describe downregulation and desensitization as phenomena that make the systems more resilient in responding to ligand perturbations thereby improving the stability of the system resting state. Conclusion Our findings suggest that in addition to serving as mechanisms for adaptation, receptor downregulation and desensitization can play a critical role in temporal information

Modulating Estrogen Receptor-related Receptor-α Activity Inhibits Cell Proliferation*

OpenAIRE

Bianco, Stéphanie; Lanvin, Olivia; Tribollet, Violaine; Macari, Claire; North, Sophie; Vanacker, Jean-Marc

2009-01-01

High expression of the estrogen receptor-related receptor (ERR)-α in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRα reduces the proliferation of various cell lines and blocks the G1/S transition of the cell cycle in an ERR...

Receptor binding properties and antinociceptive effects of chimeric peptides consisting of a micro-opioid receptor agonist and an ORL1 receptor antagonist.

Science.gov (United States)

Kawano, Susumu; Ito, Risa; Nishiyama, Miharu; Kubo, Mai; Matsushima, Tomoko; Minamisawa, Motoko; Ambo, Akihiro; Sasaki, Yusuke

2007-07-01

Receptor binding properties and antinociceptive activities of chimeric peptides linked by spacers were investigated. The peptides consisted of the micro-opioid receptor ligand dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH(2)) or its analog YRFB (Tyr-D-Arg-Phe-betaAla-NH(2)) linked to the ORL1 receptor ligand Ac-Arg-Tyr-Tyr-Arg-Ile-Lys-NH(2) (Ac-RYYRIK-NH(2)). All chimeric peptides were found to possess high receptor binding affinities for both micro-opioid and ORL1 receptors in mouse brain membranes although their binding affinities for both receptors in spinal membranes were significantly lower. Among them, chimeric peptide 2, which consists of dermorphin and Ac-RYYRIK-NH(2) connected by a long spacer, had the highest binding affinity towards both receptors. In the tail-flick test following intrathecal (i.t.) administration to mice, all chimeric peptides showed potent and dose-dependent antinociceptive activities with an ED(50) of 1.34-4.51 (pmol/mouse), nearly comparable to dermorphin alone (ED(50); 1.08 pmol/mouse). In contrast to their micro-opioid receptor binding profiles, intracerebroventricular (i.c.v.) administration of the chimeric peptides resulted in much less potent antinociceptive activity (ED(50) 5.55-100peptides, and the regulation of mu-opioid receptor-mediated antinociception in brain. The present chimeric peptides may be useful as pharmacological tools for studies on micro-opioid receptor/ORL1 receptor heterodimers.

Glutamate receptor agonists

DEFF Research Database (Denmark)

Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

2011-01-01

The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

Cocaine Inhibits Dopamine D2 Receptor Signaling via Sigma-1-D2 Receptor Heteromers

Science.gov (United States)

Navarro, Gemma; Moreno, Estefania; Bonaventura, Jordi; Brugarolas, Marc; Farré, Daniel; Aguinaga, David; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carmen; Ferre, Sergi

2013-01-01

Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2

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Kuwasako, Kenji, E-mail: kuwasako@fc.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kitamura, Kazuo; Nagata, Sayaka; Hikosaka, Tomomi [Division of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

2010-02-12

Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [{sup 125}I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100 ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2 complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser{sup 449} to Ser{sup 467} were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.

Prostaglandin Receptor Signaling in Disease

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Toshiyuki Matsuoka

2007-01-01

Full Text Available Prostanoids, consisting of the prostaglandins (PGs and the thromboxanes (TXs, are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2α, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP, four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4, the PGF receptor (FP, PGI receptor (IP, and TXA receptor (TP. Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors.

Science.gov (United States)

Linares, Andrea; Couling, Leena E; Carrera, Eduardo J; Speth, Robert C

2016-06-07

This protocol describes receptor binding patterns for Angiotensin II (Ang II) in the rat brain using a radioligand specific for Ang II receptors to perform receptor autoradiographic mapping. Tissue specimens are harvested and stored at -80 °C. A cryostat is used to coronally section the tissue (brain) and thaw-mount the sections onto charged slides. The slide-mounted tissue sections are incubated in (125)I-SI-Ang II to radiolabel Ang II receptors. Adjacent slides are separated into two sets: 'non-specific binding' (NSP) in the presence of a receptor saturating concentration of non-radiolabeled Ang II, or an AT1 Ang II receptor subtype (AT1R) selective Ang II receptor antagonist, and 'total binding' with no AT1R antagonist. A saturating concentration of AT2 Ang II receptor subtype (AT2R) antagonist (PD123319, 10 µM) is also present in the incubation buffer to limit (125)I-SI-Ang II binding to the AT1R subtype. During a 30 min pre-incubation at ~22 °C, NSP slides are exposed to 10 µM PD123319 and losartan, while 'total binding' slides are exposed to 10 µM PD123319. Slides are then incubated with (125)I-SI-Ang II in the presence of PD123319 for 'total binding', and PD123319 and losartan for NSP in assay buffer, followed by several 'washes' in buffer, and water to remove salt and non-specifically bound radioligand. The slides are dried using blow-dryers, then exposed to autoradiography film using a specialized film and cassette. The film is developed and the images are scanned into a computer for visual and quantitative densitometry using a proprietary imaging system and a spreadsheet. An additional set of slides are thionin-stained for histological comparisons. The advantage of using receptor autoradiography is the ability to visualize Ang II receptors in situ, within a section of a tissue specimen, and anatomically identify the region of the tissue by comparing it to an adjacent histological reference section.

Expression of GABAergic receptors in mouse taste receptor cells.

Directory of Open Access Journals (Sweden)

Margaret R Starostik

Full Text Available BACKGROUND: Multiple excitatory neurotransmitters have been identified in the mammalian taste transduction, with few studies focused on inhibitory neurotransmitters. Since the synthetic enzyme glutamate decarboxylase (GAD for gamma-aminobutyric acid (GABA is expressed in a subset of mouse taste cells, we hypothesized that other components of the GABA signaling pathway are likely expressed in this system. GABA signaling is initiated by the activation of either ionotropic receptors (GABA(A and GABA(C or metabotropic receptors (GABA(B while it is terminated by the re-uptake of GABA through transporters (GATs. METHODOLOGY/PRINCIPAL FINDINGS: Using reverse transcriptase-PCR (RT-PCR analysis, we investigated the expression of different GABA signaling molecules in the mouse taste system. Taste receptor cells (TRCs in the circumvallate papillae express multiple subunits of the GABA(A and GABA(B receptors as well as multiple GATs. Immunocytochemical analyses examined the distribution of the GABA machinery in the circumvallate papillae. Both GABA(A-and GABA(B- immunoreactivity were detected in the peripheral taste receptor cells. We also used transgenic mice that express green fluorescent protein (GFP in either the Type II taste cells, which can respond to bitter, sweet or umami taste stimuli, or in the Type III GAD67 expressing taste cells. Thus, we were able to identify that GABAergic receptors are expressed in some Type II and Type III taste cells. Mouse GAT4 labeling was concentrated in the cells surrounding the taste buds with a few positively labeled TRCs at the margins of the taste buds. CONCLUSIONS/SIGNIFICANCE: The presence of GABAergic receptors localized on Type II and Type III taste cells suggests that GABA is likely modulating evoked taste responses in the mouse taste bud.

AMPA receptor ligands

DEFF Research Database (Denmark)

Strømgaard, Kristian; Mellor, Ian

2004-01-01

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.

Science.gov (United States)

Cervetto, Chiara; Venturini, Arianna; Passalacqua, Mario; Guidolin, Diego; Genedani, Susanna; Fuxe, Kjell; Borroto-Esquela, Dasiel O; Cortelli, Pietro; Woods, Amina; Maura, Guido; Marcoli, Manuela; Agnati, Luigi F

2017-01-01

Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders. © 2016 International Society for Neurochemistry.

N-glycosylation of the β2 adrenergic receptor regulates receptor function by modulating dimerization.

Science.gov (United States)

Li, Xiaona; Zhou, Mang; Huang, Wei; Yang, Huaiyu

2017-07-01

N-glycosylation is a common post-translational modification of G-protein-coupled receptors (GPCRs). However, it remains unknown how N-glycosylation affects GPCR signaling. β 2 adrenergic receptor (β 2 AR) has three N-glycosylation sites: Asn6, Asn15 at the N-terminus, and Asn187 at the second extracellular loop (ECL2). Here, we show that deletion of the N-glycan did not affect receptor expression and ligand binding. Deletion of the N-glycan at the N-terminus rather than Asn187 showed decreased effects on isoproterenol-promoted G-protein-dependent signaling, β-arrestin2 recruitment, and receptor internalization. Both N6Q and N15Q showed decreased receptor dimerization, while N187Q did not influence receptor dimerization. As decreased β 2 AR homodimer accompanied with reduced efficiency for receptor function, we proposed that the N-glycosylation of β 2 AR regulated receptor function by influencing receptor dimerization. To verify this hypothesis, we further paid attention to the residues at the dimerization interface. Studies of Lys60 and Glu338, two residues at the receptor dimerization interface, exhibited that the K60A/E338A showed decreased β 2 AR dimerization and its effects on receptor signaling were similar to N6Q and N15Q, which further supported the importance of receptor dimerization for receptor function. This work provides new insights into the relationship among glycosylation, dimerization, and function of GPCRs. Peptide-N-glycosidase F (PNGase F, EC 3.2.2.11); endo-β-N-acetylglucosaminidase A (Endo-A, EC 3.2.1.96). © 2017 Federation of European Biochemical Societies.

Prognostic Value of Estrogen Receptor alpha and Progesterone Receptor Conversion in Distant Breast Cancer Metastases

NARCIS (Netherlands)

Hoefnagel, Laurien D. C.; Moelans, Cathy B.; Meijer, S. L.; van Slooten, Henk-Jan; Wesseling, Pieter; Wesseling, Jelle; Westenend, Pieter J.; Bart, Joost; Seldenrijk, Cornelis A.; Nagtegaal, Iris D.; Oudejans, Joost; van der Valk, Paul; van Gils, Carla H.; van der Wall, Elsken; van Diest, Paul J.

2012-01-01

BACKGROUND: Changes in the receptor profile of primary breast cancers to their metastases (receptor conversion) have been described for the estrogen receptor alpha (ER alpha) and progesterone receptor (PR). The purpose of this study was to evaluate the impact of receptor conversion for ER alpha and

Surveillance study of vector species on board passenger ships, Risk factors related to infestations

Directory of Open Access Journals (Sweden)

Hatzoglou Chrissi

2008-03-01

Full Text Available Abstract Background Passenger ships provide conditions suitable for the survival and growth of pest populations. Arthropods and rodents can gain access directly from the ships' open spaces, can be carried in shiploads, or can be found on humans or animals as ectoparasites. Vectors on board ships may contaminate stored foods, transmit illness on board, or, introduce diseases in new areas. Pest species, ship areas facilitating infestations, and different risk factors related to infestations were identified in 21 ferries. Methods 486 traps for insects and rodents were placed in 21 ferries. Archives of Public Health Authorities were reviewed to identify complaints regarding the presence of pest species on board ferries from 1994 to 2004. A detail questionnaire was used to collect data on ship characteristics and pest control practices. Results Eighteen ferries were infested with flies (85.7%, 11 with cockroaches (52.3%, three with bedbugs, and one with fleas. Other species had been found on board were ants, spiders, butterflies, beetles, and a lizard. A total of 431 Blattella germanica species were captured in 28 (9.96% traps, and 84.2% of them were nymphs. One ship was highly infested. Cockroach infestation was negatively associated with ferries in which Hazard Analysis Critical Control Point system was applied to ensure food safety on board (Relative Risk, RR = 0.23, p = 0.03, and positively associated with ferries in which cockroaches were observed by crew (RR = 4.09, p = 0.007, no cockroach monitoring log was kept (RR = 5.00, p = 0.02, and pesticide sprays for domestic use were applied by crew (RR = 4.00, p = 0.05. Cockroach infested ships had higher age (p = 0.03. Neither rats nor mice were found on any ship, but three ferries had been infested with a rodent in the past. Conclusion Integrated pest control programs should include continuing monitoring for a variety of pest species in different ship locations; pest control measures should be more

Microarray-Based Determination of Estrogen Receptor, Progesterone Receptor, and HER2 Receptor Status in Breast Cancer

NARCIS (Netherlands)

Roepman, Paul; Horlings, Hugo M.; Krijgsman, Oscar; Kok, Marleen; Bueno-de-Mesquita, Jolien M.; Bender, Richard; Linn, Sabine C.; Glas, Annuska M.; van de Vijver, Marc J.

2009-01-01

Purpose: The level of estrogen receptor (ER), progesterone receptor (PR), and HER2 aids in the determination of prognosis and treatment of breast cancer. Immunohistochemistry is currently the predominant method for assessment, but differences in methods and interpretation can substantially affect

The Orphan Nuclear Receptor TR4 Is a Vitamin A-activated Nuclear Receptor

Energy Technology Data Exchange (ETDEWEB)

Zhou, X. Edward; Suino-Powell, Kelly M.; Xu, Yong; Chan, Cee-Wah; Tanabe, Osamu; Kruse, Schoen W.; Reynolds, Ross; Engel, James Douglas; Xu, H. Eric (Michigan-Med); (Van Andel)

2015-11-30

Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation. The ligand binding pocket of TR4 is filled by the C-terminal half of helix 10, and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibits constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4.

Soman- or kainic acid-induced convulsions decrease muscarinic receptors but not benzodiazepine receptors

International Nuclear Information System (INIS)

Churchill, L.; Pazdernik, T.L.; Cross, R.S.; Nelson, S.R.; Samson, F.E.

1990-01-01

[3H]Quinuclidinyl benzilate (QNB) binding to muscarinic receptors decreased in the rat forebrain after convulsions induced by a single dose of either soman, a potent inhibitor of acetylcholinesterase, or kainic acid, an excitotoxin. A Rosenthal plot revealed that the receptors decreased in number rather than affinity. When the soman-induced convulsions were blocked, the decrease in muscarinic receptors at 3 days was less extensive than when convulsions occurred and at 10 days they approached control levels in most of the brain areas. The most prominent decrements in QNB binding were in the piriform cortex where the decline in QNB binding is probably related to the extensive convulsion-associated neuropathology. The decrements in QNB binding after convulsions suggest that the convulsive state leads to a down-regulation of muscarinic receptors in some brain areas. In contrast to the decrease in QNB binding after convulsions, [3H]flunitrazepam binding to benzodiazepine receptors did not change even in the piriform cortex where the loss in muscarinic receptors was most prominent. Thus, it appears that those neuronal processes that bear muscarinic receptors are more vulnerable to convulsion-induced change than those with benzodiazepine receptors

Cooperative ethylene receptor signaling

OpenAIRE

Liu, Qian; Wen, Chi-Kuang

2012-01-01

The gaseous plant hormone ethylene is perceived by a family of five ethylene receptor members in the dicotyledonous model plant Arabidopsis. Genetic and biochemical studies suggest that the ethylene response is suppressed by ethylene receptor complexes, but the biochemical nature of the receptor signal is unknown. Without appropriate biochemical measures to trace the ethylene receptor signal and quantify the signal strength, the biological significance of the modulation of ethylene responses ...

Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

International Nuclear Information System (INIS)

Waser, Beatrice; Reubi, Jean Claude

2014-01-01

Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the 125 iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer 125 I-GLP-1(7-36)amide. Receptor autoradiography studies with 125 I-GLP-1(7-36)amide agonist or 125 I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist 125 I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer 125 I-GLP-1(7-36)amide. For comparison, 125 I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with 125 I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

International Nuclear Information System (INIS)

Pires, L.A.; Hegg, R.; Freitas, F.R.; Tavares, E.R.; Almeida, C.P.; Baracat, E.C.; Maranhão, R.C.

2012-01-01

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy

Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

Energy Technology Data Exchange (ETDEWEB)

Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland)

2014-06-15

Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the {sup 125}iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer {sup 125}I-GLP-1(7-36)amide. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist {sup 125}I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer {sup 125}I-GLP-1(7-36)amide. For comparison, {sup 125}I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with {sup 125}I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

Dengue virus receptor

OpenAIRE

Hidari, Kazuya I.P.J.; Suzuki, Takashi

2011-01-01

Dengue virus is an arthropod-borne virus transmitted by Aedes mosquitoes. Dengue virus causes fever and hemorrhagic disorders in humans and non-human primates. Direct interaction of the virus introduced by a mosquito bite with host receptor molecule(s) is crucial for virus propagation and the pathological progression of dengue diseases. Therefore, elucidation of the molecular mechanisms underlying the interaction between dengue virus and its receptor(s) in both humans and mosquitoes is essent...

Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

NARCIS (Netherlands)

Douma, B. R.; Korte, S. M.; Buwalda, B.; La Fleur, S. E.; Bohus, B.; Luiten, P. G.

1998-01-01

Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

Repeated blockade of mineralocorticoid receptors, but not of glucocorticoid receptors impairs food rewarded spatial learning

NARCIS (Netherlands)

Douma, BRK; Korte, SM; Buwalda, B; la Fleur, SE; Bohus, B; Luiten, PGM

Corticosteroids from the adrenal cortex influence a variety of behaviours including cognition, learning and memory. These hormones act via two intracellular receptors, the mineralo-corticoid receptor (MR) and the glucocorticoid receptor (GR). These two receptor types display a high concentration and

Dust and airborne exposure to allergens derived from cockroach (Blattella germanica) in low-cost public housing in Strasbourg (France).

Science.gov (United States)

de Blay, F; Sanchez, J; Hedelin, G; Perez-Infante, A; Vérot, A; Chapman, M; Pauli, G

1997-01-01

Although a strong association between allergy to cockroach (CR) and asthma has been observed in the United States and Asia, there are little data about the extent of exposure to CR allergen in Europe. To determine the levels of CR allergens in dust samples from apartments in Strasbourg and to determine the concentration and size of CR allergens in the air. Nine apartments in a public housing complex were chosen on the basis of visual evidence of CR infestation. Levels of CR allergens (Bla g 1 and Bla g 2) in kitchen and mattress dust samples were measured by immunoassay with the use of monoclonal antibodies. Air was sampled for 3 to 8 hours in the kitchen under undisturbed conditions, during artificial disturbance, and during normal domestic activity by using an impinger and a parallel glass fiber filter and at flow rates of 2 to 20 L/min. Airborne CR and mite allergens were measured concurrently in the bedroom of one apartment before, during, and after artificial disturbance. High levels of Bla g 1 and Bla g 2 were found in kitchen dust from the nine apartments (geometric means of 3919 U/gm [range 530 to 14306 U/gm] and 497 U/gm [range 73 to 1946 U/gm], respectively). Under undisturbed conditions, airborne CR allergens were not detectable in any of the apartments. During vigorous artificial disturbance, Bla g 1 and Bla g 2 were detectable in air samples from seven apartments (geometric means of 4.5 U/m3 [range 0.7 to 17.2 U/m3] and 1.0 U/m3 [range 0.4 to 3.4 U/m3], respectively). Both allergens were predominantly collected on the first stage of the impinger, and 76% to 80% of the airborne allergen was associated with particles greater than 10 microns in diameter. The levels were significantly higher than those collected on the second or third stages of the impinger (p low-cost public housing in Strasbourg can be as high as or higher than the levels measured in towns in the United States. CR allergens become airborne during disturbance and are primarily associated

Functional relevance of G-protein-coupled-receptor-associated proteins, exemplified by receptor-activity-modifying proteins (RAMPs).

Science.gov (United States)

Fischer, J A; Muff, R; Born, W

2002-08-01

The calcitonin (CT) receptor (CTR) and the CTR-like receptor (CRLR) are close relatives within the type II family of G-protein-coupled receptors, demonstrating sequence identity of 50%. Unlike the interaction between CT and CTR, receptors for the related hormones and neuropeptides amylin, CT-gene-related peptide (CGRP) and adrenomedullin (AM) require one of three accessory receptor-activity-modifying proteins (RAMPs) for ligand recognition. An amylin/CGRP receptor is revealed when CTR is co-expressed with RAMP1. When complexed with RAMP3, CTR interacts with amylin alone. CRLR, initially classed as an orphan receptor, is a CGRP receptor when co-expressed with RAMP1. The same receptor is specific for AM in the presence of RAMP2. Together with human RAMP3, CRLR defines an AM receptor, and with mouse RAMP3 it is a low-affinity CGRP/AM receptor. CTR-RAMP1, antagonized preferentially by salmon CT-(8-32) and not by CGRP-(8-37), and CRLR-RAMP1, antagonized by CGRP-(8-37), are two CGRP receptor isotypes. Thus amylin and CGRP interact specifically with heterodimeric complexes between CTR and RAMP1 or RAMP3, and CGRP and AM interact with complexes between CRLR and RAMP1, RAMP2 or RAMP3.

Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor.

Science.gov (United States)

Cunningham, Margaret R; Aungraheeta, Riyaad; Mundell, Stuart J

2017-07-05

Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y 1 and P2Y 12 ), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y 12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems. Copyright © 2017. Published by Elsevier B.V.

Bla g 1 allergen levels in Zagreb area household dust.

Science.gov (United States)

Prester, Ljerka; Macan, Jelena

2011-03-01

Cockroach allergy is a health problem in many parts of the world. In urban environments, indoor exposure to cockroach allergens involves a risk of asthma. The aim of this study was to measure the mass fraction of Bla g 1, a major allergen of the German cockroach (Blatella germanica) in 30 house samples, collected at random from Zagreb area households, Croatia. Dust samples were collected on cellulose filters by vacuuming living rooms floors. After extraction, Bla g 1 was detected using the commercial enzyme-linked immunosorbent assay (ELISA). Only four of the thirty households had detectable Bla g 1 levels, and only in one was its concentration higher than 2.0 U g(-1), the threshold associated with sensitisation. The Bla g 1 ELISA proved highly sensitive, with the detection limit of 0.12 U g(-1). The within- and between-assay imprecision was 8.9 % and 14.4 %, respectively, and accuracy 85 % to 120 %. Low Bla g 1 levels in the household dust support previously reported low prevalence of skin sensitisation to B. germanica among Zagreb residents. Further monitoring should reveal if there are differences in cockroach allergen exposure and sensitisation between households from other geographic areas in Croatia.

Acetylcholine receptor antibody

Science.gov (United States)

... medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood of ...

L-glutamate Receptor In Paramecium

Science.gov (United States)

Bernal-Martínez, Juan; Ortega-Soto, Arturo

2004-09-01

Behavioral, electrophysiological and biochemical experiments were performed in order to establish the presence of a glutamate receptor in the ciliate Paramecium. It was found that an AMPA/KA receptor is functionally expressed in Paramecium and that this receptor is immunologically and fillogenetically related to the AMPA/KA receptor present in vertebrates.

Do receptors get pregnant too? Adrenergic receptor alterations in human pregnancy.

Science.gov (United States)

Smiley, R M; Finster, M

1996-01-01

In this review we discuss adrenergic receptor number and function during pregnancy, with emphasis on evidence that pregnancy results in specific receptor alterations from the nonpregnant state. Changes in adrenergic receptor function or distribution in vascular smooth muscle may be in part responsible for the decreased vascular responsiveness seen in human pregnancy, and the lack of the normal alterations may be a part of the syndromes of gestational hypertension, including preeclampsia-eclampsia. The onset of labor may be influenced by adrenergic modulation, and receptor or postreceptor level molecular alterations may trigger or facilitate normal or preterm labor. Human studies are emphasized when possible to assess the role of adrenergic signal transduction regulation in the physiology and pathophysiology of normal and complicated human pregnancy.

Melatonin Receptor Genes in Vertebrates

Directory of Open Access Journals (Sweden)

Hua Dong Yin

2013-05-01

Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

Clinical and Genomic Crosstalk between Glucocorticoid Receptor and Estrogen Receptor α In Endometrial Cancer

Directory of Open Access Journals (Sweden)

Jeffery M. Vahrenkamp

2018-03-01

Full Text Available Summary: Steroid hormone receptors are simultaneously active in many tissues and are capable of altering each other’s function. Estrogen receptor α (ER and glucocorticoid receptor (GR are expressed in the uterus, and their ligands have opposing effects on uterine growth. In endometrial tumors with high ER expression, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia. We observed low genomic-binding site overlap when ER and GR are induced with their respective ligands; however, upon simultaneous induction they co-occupy more sites. GR binding is altered significantly by estradiol with GR recruited to ER-bound loci that become more accessible upon estradiol induction. Gene expression responses to co-treatment were more similar to estradiol but with additional regulated genes. Our results suggest phenotypic and molecular interplay between ER and GR in endometrial cancer. : Estrogen receptor α (ER and glucocorticoid receptor (GR are expressed in the uterus and have differential effects on growth. Vahrenkamp et al. find that expression of both receptors is associated with poor outcome in endometrial cancer and that simultaneous induction of ER and GR leads to molecular interplay between the receptors. Keywords: estrogen receptor, glucocorticoid receptor, endometrial cancer

Receptor binding radiotracers for the angiotensin II receptor: radioiodinated [Sar1, Ile8]angiotensin II

International Nuclear Information System (INIS)

Gibson, R.E.; Beauchamp, H.T.; Fioravanti, C.; Brenner, N.; Burns, H.D.

1994-01-01

The potential for imaging the angiotensin II receptor was evaluated using the radioiodinated peptide antagonist [ 125 I][Sar 1 , Ile 8 ]angiotensin II. The radioligand provides a receptor-mediated signal in several tissues in rat (kidneys, adrenal and liver). The receptor-mediated signal of 3% ID/g kidney cortex should be sufficient to permit imaging, at least via SPECT. The radiotracer is sensitive to reductions in receptor concentration and can be used to define in vivo dose-occupancy curves of angiotensin II receptor ligands. Receptor-mediated images of [ 123 I][Sar 1 , Ile 8 ]angiotensin II were obtained in the rat kidney and Rhesus monkey liver. (author)

The lactate receptor, G-protein-coupled receptor 81/hydroxycarboxylic acid receptor 1

DEFF Research Database (Denmark)

Morland, Cecilie; Lauritzen, Knut Huso; Puchades, Maja

2015-01-01

We have proposed that lactate is a “volume transmitter” in the brain and underpinned this by showing that the lactate receptor, G-protein-coupled receptor 81 (GPR81, also known as HCA1 or HCAR1), which promotes lipid storage in adipocytes, is also active in the mammalian brain. This includes......, energy metabolism, and energy substrate availability, including a glucose- and glycogen-saving response. HCAR1 may contribute to optimizing the cAMP concentration. For instance, in the prefrontal cortex, excessively high cAMP levels are implicated in impaired cognition in old age, fatigue, stress...

Adenosine receptor desensitization and trafficking.

Science.gov (United States)

Mundell, Stuart; Kelly, Eamonn

2011-05-01

As with the majority of G-protein-coupled receptors, all four of the adenosine receptor subtypes are known to undergo agonist-induced regulation in the form of desensitization and trafficking. These processes can limit the ability of adenosine receptors to couple to intracellular signalling pathways and thus reduce the ability of adenosine receptor agonists as well as endogenous adenosine to produce cellular responses. In addition, since adenosine receptors couple to multiple signalling pathways, these pathways may desensitize differentially, while the desensitization of one pathway could even trigger signalling via another. Thus, the overall picture of adenosine receptor regulation can be complex. For all adenosine receptor subtypes, there is evidence to implicate arrestins in agonist-induced desensitization and trafficking, but there is also evidence for other possible forms of regulation, including second messenger-dependent kinase regulation, heterologous effects involving G proteins, and the involvement of non-clathrin trafficking pathways such as caveolae. In this review, the evidence implicating these mechanisms is summarized for each adenosine receptor subtype, and we also discuss those issues of adenosine receptor regulation that remain to be resolved as well as likely directions for future research in this field. Copyright © 2010 Elsevier B.V. All rights reserved.

Cocaine Disrupts Histamine H3 Receptor Modulation of Dopamine D1 Receptor Signaling: σ1-D1-H3 Receptor Complexes as Key Targets for Reducing Cocaine's Effects

Science.gov (United States)

Moreno, Estefanía; Moreno-Delgado, David; Navarro, Gemma; Hoffmann, Hanne M.; Fuentes, Silvia; Rosell-Vilar, Santi; Gasperini, Paola; Rodríguez-Ruiz, Mar; Medrano, Mireia; Mallol, Josefa; Cortés, Antoni; Casadó, Vicent; Lluís, Carme; Ferré, Sergi; Ortiz, Jordi; Canela, Enric

2014-01-01

The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine binding to σ1-D1-H3 receptor complexes. The cocaine-mediated disruption leaves an uninhibited D1 receptor that activates Gs, freely recruits β-arrestin, increases p-ERK 1/2 levels, and induces cell death when over activated. Using in vitro assays with transfected cells and in ex vivo experiments using both rats acutely treated or self-administered with cocaine along with mice depleted of σ1 receptor, we show that blockade of σ1 receptor by an antagonist restores the protective H3 receptor-mediated brake on D1 receptor signaling and prevents the cell death from elevated D1 receptor signaling. These findings suggest that a combination therapy of σ1R antagonists with H3 receptor agonists could serve to reduce some effects of cocaine. PMID:24599455

Receptor studies in biological psychiatry

International Nuclear Information System (INIS)

Fujiwara, Yutaka

1992-01-01

Recent advances in the pharmacological treatment of endogenous psychosis have led to the development of biological studies in psychiatry. Studies on neurotransmitter receptors were reviewed in order to apply positron-emission tomograph (PET) for biological psychiatry. The dopamine (DA) hypothesis for schizophrenia was advanced on the basis of the observed effects of neuroleptics and methamphetamine, and DA(D 2 ) receptor supersensitivity measured by PET and receptor binding in the schizophrenic brain. The clinical potencies of neuroleptics for schizophrenia were correlated with their abilities to inhibit the D 2 receptor, and not other receptors. The σ receptor was expected to be a site of antipsychotic action. However, the potency of drugs action on it was not correlated with clinical efficacy. Haloperidol binds with high affinity to the σ receptor, which may mediate acute dystonia, an extrapyramidal side effect of neuroleptics. Behavioral and neurochemical changes induced by methamphetamine treatment were studied as an animal model of schizophrenia, and both a decrease of D 2 receptor density and an increase of DA release were detected. The monoamine hypothesis for manic-depressive psychosis was advanced on the basis of the effect of reserpine, monoamine oxidase inhibitor and antidepressants. 3 H-clonidine binding sites were increased in platelet membranes of depressive patients, 3 H-imipramine binding sites were decreased. The GABA A receptor is the target site for the action of anxiolytics and antiepileptics such as benzodiazepines and barbiturates. Recent developments in molecular biology techniques have revealed the structure of receptor proteins, which are classified into two receptor families, the G-protein coupled type (D 2 ) and the ion-channel type (GABA A ). (J.P.N.)

Arrestin scaffolds NHERF1 to the P2Y12 receptor to regulate receptor internalization.

Science.gov (United States)

Nisar, Shaista P; Cunningham, Margaret; Saxena, Kunal; Pope, Robert J; Kelly, Eamonn; Mundell, Stuart J

2012-07-13

We have recently shown in a patient with mild bleeding that the PDZ-binding motif of the platelet G protein-coupled P2Y(12) receptor (P2Y(12)R) is required for effective receptor traffic in human platelets. In this study we show for the first time that the PDZ motif-binding protein NHERF1 exerts a major role in potentiating G protein-coupled receptor (GPCR) internalization. NHERF1 interacts with the C-tail of the P2Y(12)R and unlike many other GPCRs, NHERF1 interaction is required for effective P2Y(12)R internalization. In vitro and prior to agonist stimulation P2Y(12)R/NHERF1 interaction requires the intact PDZ binding motif of this receptor. Interestingly on receptor stimulation NHERF1 no longer interacts directly with the receptor but instead binds to the receptor via the endocytic scaffolding protein arrestin. These findings suggest a novel model by which arrestin can serve as an adaptor to promote NHERF1 interaction with a GPCR to facilitate effective NHERF1-dependent receptor internalization.

A candidate pheromone receptor and two odorant receptors of the hawkmoth Manduca sexta.

Science.gov (United States)

Patch, Harland M; Velarde, Rodrigo A; Walden, Kimberly K O; Robertson, Hugh M

2009-05-01

In this study, we cloned and characterized three Manduca sexta odorant receptors (ORs). One receptor is a putative pheromone receptor expressed exclusively in a cell associated with male-specific type-I trichoid sensilla. We describe the results of real-time PCR (RT-PCR) and quantitative real-time PCR (qRT-PCR) experiments that show MsextaOR1 is expressed only in male antennae. In situ hybridization labels a single cell associated with type-1 trichoid sensilla, which houses two neurons that have been previously determined to respond to the major components of the pheromone blend. The second receptor, MsextaOR2, was discovered using degenerate primers designed to conserved motifs of a unique group ORs that share as much as 88% identity. Comparison of RT-PCR, qRT-PCR, and in situ hybridization results with those of ORs in the Drosophila melanogaster Or83b subfamily shows a strong sequence and expression pattern similarity. The third receptor, MsextaOR3, was found by 5'-end sequencing of a normalized and subtracted cDNA library from male M. sexta antennae. RT-PCR and qRT-PCR show that this receptor is expressed only in male and female antennae. These are the first ORs, including a putative pheromone receptor, to be described from M. sexta.

Transcriptional targets shared by estrogen receptor- related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ERbeta.

Science.gov (United States)

Vanacker, J M; Pettersson, K; Gustafsson, J A; Laudet, V

1999-01-01

The physiological activities of estrogens are thought to be mediated by specific nuclear receptors, ERalpha and ERbeta. However, certain tissues, such as the bone, that are highly responsive to estrogens only express a low level of these receptors. Starting from this apparent contradiction, we have evaluated the potentials of two related receptors ERRalpha and ERRbeta to intervene in estrogen signaling. ERalpha, ERRalpha and ERRbeta bind to and activate transcription through both the classical estrogen response element (ERE) and the SF-1 response element (SFRE). In contrast, ERbeta DNA-binding and transcriptional activity is restricted to the ERE. Accordingly, the osteopontin gene promoter is stimulated through SFRE sequences, by ERRalpha as well as by ERalpha, but not by ERbeta. Analysis of the cross-talk within the ER/ERR subgroup of nuclear receptors thus revealed common targets but also functional differences between the two ERs. PMID:10428965

Flavivirus Entry Receptors: An Update

Directory of Open Access Journals (Sweden)

Manuel Perera-Lecoin

2013-12-01

Full Text Available Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM and TYRO3, AXL and MER (TAM. Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth.

Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor.

Science.gov (United States)

Armour, S L; Foord, S; Kenakin, T; Chen, W J

1999-12-01

Receptor-activity-modifying proteins (RAMPs) are a family of single transmembrane domain proteins shown to be important for the transport and ligand specificity of the calcitonin gene-related peptide (CGRP) receptor. In this report, we describe the analysis of pharmacological properties of the human calcitonin receptor (hCTR) coexpressed with different RAMPs with the use of the Xenopus laevis melanophore expression system. We show that coexpression of RAMP3 with human calcitonin receptor changed the relative potency of hCTR to human calcitonin (hCAL) and rat amylin. RAMP1 and RAMP2, in contrast, had little effect on the change of hCTR potency to hCAL or rat amylin. When coexpressed with RAMP3, hCTR reversed the relative potency by a 3.5-fold loss in sensitivity to hCAL and a 19-fold increase in sensitivity to rat amylin. AC66, an inverse agonist, produced apparent simple competitive antagonism of hCAL and rat amylin, as indicated by linear Schild regressions. The potency of AC66 was changed in the blockade of rat amylin but not hCAL responses with RAMP3 coexpression. The mean pK(B) for AC66 to hCAL was 9.4 +/- 0.3 without RAMP3 and 9.45 +/- 0.07 with RAMP3. For the antagonism of AC66 to rat amylin, the pK(B) was 9.25 +/- 0.15 without RAMP3 and 8.2 +/- 0.35 with RAMP3. The finding suggests that RAMP3 might modify the active states of calcitonin receptor in such a way as to create a new receptor phenotype that is "amylin-like." Irrespective of the physiological association of the new receptor species, the finding that a coexpressed membrane protein can completely change agonist and antagonist affinities for a receptor raises implications for screening in recombinant receptor systems.

Serotonin 5-HT4 receptors and forebrain cholinergic system: receptor expression in identified cell populations.

Science.gov (United States)

Peñas-Cazorla, Raúl; Vilaró, M Teresa

2015-11-01

Activation of serotonin 5-HT4 receptors has pro-cognitive effects on memory performance. The proposed underlying neurochemical mechanism is the enhancement of acetylcholine release in frontal cortex and hippocampus elicited by 5-HT4 agonists. Although 5-HT4 receptors are present in brain areas related to cognition, e.g., hippocampus and cortex, the cellular localization of the receptors that might modulate acetylcholine release is unknown at present. We have analyzed, using dual label in situ hybridization, the cellular localization of 5-HT4 receptor mRNA in identified neuronal populations of the rat basal forebrain, which is the source of the cholinergic innervation to cortex and hippocampus. 5-HT4 receptor mRNA was visualized with isotopically labeled oligonucleotide probes, whereas cholinergic, glutamatergic, GABAergic and parvalbumin-synthesizing neurons were identified with digoxigenin-labeled oligonucleotide probes. 5-HT4 receptor mRNA was not detected in the basal forebrain cholinergic cell population. In contrast, basal forebrain GABAergic, parvalbumin synthesizing, and glutamatergic cells contained 5-HT4 receptor mRNA. Hippocampal and cortical glutamatergic neurons also express this receptor. These results indicate that 5-HT4 receptors are not synthesized by cholinergic cells, and thus would be absent from cholinergic terminals. In contrast, several non-cholinergic cell populations within the basal forebrain and its target hippocampal and cortical areas express these receptors and are thus likely to mediate the enhancement of acetylcholine release elicited by 5-HT4 agonists.

Stargazin Modulation of AMPA Receptors

Directory of Open Access Journals (Sweden)

Sana A. Shaikh

2016-10-01

Full Text Available Fast excitatory synaptic signaling in the mammalian brain is mediated by AMPA-type ionotropic glutamate receptors. In neurons, AMPA receptors co-assemble with auxiliary proteins, such as stargazin, which can markedly alter receptor trafficking and gating. Here, we used luminescence resonance energy transfer measurements to map distances between the full-length, functional AMPA receptor and stargazin expressed in HEK293 cells and to determine the ensemble structural changes in the receptor due to stargazin. In addition, we used single-molecule fluorescence resonance energy transfer to study the structural and conformational distribution of the receptor and how this distribution is affected by stargazin. Our nanopositioning data place stargazin below the AMPA receptor ligand-binding domain, where it is well poised to act as a scaffold to facilitate the long-range conformational selection observations seen in single-molecule experiments. These data support a model of stargazin acting to stabilize or select conformational states that favor activation.

Photo-antagonism of the GABAA receptor.

Science.gov (United States)

Mortensen, Martin; Iqbal, Favaad; Pandurangan, Arun P; Hannan, Saad; Huckvale, Rosemary; Topf, Maya; Baker, James R; Smart, Trevor G

2014-07-29

Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation.

Scavenger receptors in homeostasis and immunity.

Science.gov (United States)

Canton, Johnathan; Neculai, Dante; Grinstein, Sergio

2013-09-01

Scavenger receptors were originally identified by their ability to recognize and to remove modified lipoproteins; however, it is now appreciated that they carry out a striking range of functions, including pathogen clearance, lipid transport, the transport of cargo within the cell and even functioning as taste receptors. The large repertoire of ligands recognized by scavenger receptors and their broad range of functions are not only due to the wide range of receptors that constitute this family but also to their ability to partner with various co-receptors. The ability of individual scavenger receptors to associate with different co-receptors makes their responsiveness extremely versatile. This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease.

Central alpha2 adrenergic receptors in the rat cerebral cortex: repopulation kinetics and receptor reserve

International Nuclear Information System (INIS)

Adler, C.H.

1986-01-01

The alpha 2 adrenergic receptor subtype is thought to play a role in the mechanism of action of antidepressant and antihypertensive drugs. This thesis has attempted to shed light on the regulation of central alpha 2 adrenergic receptors in the rat cerebral cortex. Repopulation kinetics analysis allows for the determination of the rate of receptor production, rate constant of degradation, and half-life of the receptor. This analysis was carried out using both radioligand binding and functional receptor assays at various times following the irreversible inactivation of central alpha 2 adrenergic receptors by in vivo administration of N-ethoxycarbonyl-2-ethyoxy-1,2-dihydroquinoline (EEDQ). Both alpha 2 agonist and antagonist ligand binding sites recovered with a t/sub 1/2/ equal to approximately 4 days. The function of alpha 2 adrenergic autoreceptors, which inhibit stimulation-evoked release of 3 H-norepinephrine ( 3 H-NE) and alpha 2 adrenergic heteroreceptors which inhibit stimulation-evoked release of 3 H-serotonin ( 3 H-5-HT) were assayed. The t/sub 1/2/ for recovery of maximal autoreceptor and heteroreceptor function was 2.4 days and 4.6 days, respectively. The demonstration of a receptor reserve is critical to the interpretation of past and future studies of the alpha 2 adrenergic receptor since it demonstrates that: (1) alterations in the number of alpha 2 adrenergic receptor binding sites cannot be extrapolated to the actual function of the alpha 2 adrenergic receptor; and (2) alterations in the number of alpha 2 receptors is not necessarily accompanied by a change in the maximum function being studied, but may only result in shifting of the dose-response curve

Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics.

Science.gov (United States)

Tsuji, Motonori; Shudo, Koichi; Kagechika, Hiroyuki

2017-03-01

Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands.

Interaction of epidermal growth factor receptors with the cytoskeleton is related to receptor clustering

NARCIS (Netherlands)

van Belzen, N.; Spaargaren, M.; Verkleij, A. J.; Boonstra, J.

1990-01-01

Recently it has been established that cytoskeleton-associated epidermal growth factor (EGF) receptors are predominantly of the high-affinity class and that EGF induces a recruitment of low-affinity receptors to the cytoskeleton. The nature of this EGF-induced receptor-cytoskeleton interaction,

Toll-like receptors and NOD-like receptors in rheumatic diseases.

LENUS (Irish Health Repository)

McCormack, William J

2012-02-01

The past 10 years have seen the description of families of receptors that drive proinflammatory cytokine production in infection and tissue injury. Two major classes have been examined in the context of inflammatory joint disease--the Toll-like receptors (TLRs) and NOD-like receptors (NLRs). TLRs such as TLR2 and TLR4 are being implicated in the pathology of rheumatoid arthritis, ankylosing spondylitis, lyme arthritis and osteoarthritis. Nalp3 has been identified as a key NLR for IL-1beta production and has been shown to have a particular role in gout. These findings present new therapeutic opportunities, possibly allowing for the replacement of biologics with small molecule inhibitors.

Olfactory Receptor Database: a sensory chemoreceptor resource

OpenAIRE

Skoufos, Emmanouil; Marenco, Luis; Nadkarni, Prakash M.; Miller, Perry L.; Shepherd, Gordon M.

2000-01-01

The Olfactory Receptor Database (ORDB) is a WWW-accessible database that has been expanded from an olfactory receptor resource to a chemoreceptor resource. It stores data on six classes of G-protein-coupled sensory chemoreceptors: (i) olfactory receptor-like proteins, (ii) vomeronasal receptors, (iii) insect olfactory receptors, (iv) worm chemoreceptors, (v) taste papilla receptors and (vi) fungal pheromone receptors. A complementary database of the ligands of these receptors (OdorDB) has bee...

Molecular characterization of opioid receptors

Energy Technology Data Exchange (ETDEWEB)

Howard, A.D.

1986-01-01

The aim of this research was to purify and characterize active opioid receptors and elucidate molecular aspects of opioid receptor heterogeneity. Purification to apparent homogeneity of an opioid binding protein from bovine caudate was achieved by solubilization in the non-ionic detergent, digitonin, followed by sequential chromatography on the opiate affinity matrix, ..beta..-naltrexylethylenediamine-CH-Sepharose 4B, and on the lectine affinity matrix, wheat germ agglutinin-agarose. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) followed by autoradiography revealed that radioiodinated purified receptor gave a single band. Purified receptor preparations showed a specific activity of 12,000-15,000 fmol of opiate bound per mg of protein. Radioiodinated human beta-endorphin (/sup 125/I-beta-end/sub H/) was used as a probe to investigate the ligand binding subunits of mu and delta opioid receptors. /sup 125/I-beta-end/sub H/ was shown to bind to a variety of opioid receptor-containing tissues with high affinity and specificity with preference for mu and delta sites, and with little, if any, binding to kappa sites. Affinity crosslinking techniques were employed to covalently link /sup 125/I-beta-end/sub H/ to opioid receptors, utilizing derivatives of bis-succinimidyl esters that are bifunctional crosslinkers with specificities for amino and sulfhydryl groups. This, and competition experiments with high type-selective ligands, permitted the assignment of two labeled peptides to their receptor types, namely a peptide of M/sub r/ = 65,000 for mu receptors and one of M/sub r/ = 53,000 for delta receptors.

Lipid raft integrity affects GABAA receptor, but not NMDA receptor modulation by psychopharmacological compounds.

Science.gov (United States)

Nothdurfter, Caroline; Tanasic, Sascha; Di Benedetto, Barbara; Uhr, Manfred; Wagner, Eva-Maria; Gilling, Kate E; Parsons, Chris G; Rein, Theo; Holsboer, Florian; Rupprecht, Rainer; Rammes, Gerhard

2013-07-01

Lipid rafts have been shown to play an important role for G-protein mediated signal transduction and the function of ligand-gated ion channels including their modulation by psychopharmacological compounds. In this study, we investigated the functional significance of the membrane distribution of NMDA and GABAA receptor subunits in relation to the accumulation of the tricyclic antidepressant desipramine (DMI) and the benzodiazepine diazepam (Diaz). In the presence of Triton X-100, which allowed proper separation of the lipid raft marker proteins caveolin-1 and flotillin-1 from the transferrin receptor, all receptor subunits were shifted to the non-raft fractions. In contrast, under detergent-free conditions, NMDA and GABAA receptor subunits were detected both in raft and non-raft fractions. Diaz was enriched in non-raft fractions without Triton X-100 in contrast to DMI, which preferentially accumulated in lipid rafts. Impairment of lipid raft integrity by methyl-β-cyclodextrine (MβCD)-induced cholesterol depletion did not change the inhibitory effect of DMI at the NMDA receptor, whereas it enhanced the potentiating effect of Diaz at the GABAA receptor at non-saturating concentrations of GABA. These results support the hypothesis that the interaction of benzodiazepines with the GABAA receptor likely occurs outside of lipid rafts while the antidepressant DMI acts on ionotropic receptors both within and outside these membrane microdomains.

Internalization of G-protein-coupled receptors: Implication in receptor function, physiology and diseases.

Science.gov (United States)

Calebiro, Davide; Godbole, Amod

2018-04-01

G protein-coupled receptors (GPCRs) are the largest family of membrane receptors and mediate the effects of numerous hormones and neurotransmitters. The nearly 1000 GPCRs encoded by the human genome regulate virtually all physiological functions and are implicated in the pathogenesis of prevalent human diseases such as thyroid disorders, hypertension or Parkinson's disease. As a result, 30-50% of all currently prescribed drugs are targeting these receptors. Once activated, GPCRs induce signals at the cell surface. This is often followed by internalization, a process that results in the transfer of receptors from the plasma membrane to membranes of the endosomal compartment. Internalization was initially thought to be mainly implicated in signal desensitization, a mechanism of adaptation to prolonged receptor stimulation. However, several unexpected functions have subsequently emerged. Most notably, accumulating evidence indicates that internalization can induce prolonged receptor signaling on intracellular membranes, which is apparently required for at least some biological effects of hormones like TSH, LH and adrenaline. These findings reveal an even stronger connection between receptor internalization and signaling than previously thought. Whereas new studies are just beginning to reveal an important physiological role for GPCR signaling after internalization and ways to exploit it for therapeutic purposes, future investigations will be required to explore its involvement in human disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

Science.gov (United States)

Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

2012-01-01

The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling

International Nuclear Information System (INIS)

Lohse, M.J.; Klotz, K.N.; Schwabe, U.

1991-01-01

It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxy-phenylisopropyladenosine [(R)-AHPIA] into the A1 adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of cellular cAMP levels. In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenylate cyclase stimulation via these receptors. This effect of (R)-AHPIA is specific for the A2 receptor and can be prevented by the adenosine receptor antagonist theophylline. Binding studies indicate that up to 90% of A2 receptors can be blocked by photoincorporation of (R)-AHPIA. However, the remaining 10-20% of A2 receptors are sufficient to mediate an adenylate cyclase stimulation of up to 50% of the control value. Similarly, the activation via these 10-20% of receptors occurs with a half-life that is only 2 times longer than that in control membranes. This indicates the presence of a receptor reserve, with respect to both the extent and the rate of adenylate cyclase stimulation. These observations require a modification of the models of receptor-adenylate cyclase coupling

The First Fifteen Years of Steroid Receptor Research in Zebrafish; Characterization and Functional Analysis of the Receptors

Directory of Open Access Journals (Sweden)

Marcel J. M. Schaaf

2017-07-01

Full Text Available Steroid hormones regulate a wide range of processes in our body, and their effects are mediated by steroid receptors. In addition to their physiological role, these receptors mediate the effects of endocrine disrupting chemicals (EDCs and are widely used targets for dugs involved in the treatment of numerous diseases, ranging from cancer to inflammatory disorders. Over the last fifteen years, the zebrafish has increasingly been used as an animal model in steroid receptor research. Orthologues of all human steroid receptor genes appear to be present in zebrafish. All zebrafish steroid receptors have been characterized in detail, and their expression patterns have been analyzed. Functional studies have been performed using morpholino knockdown of receptor expression and zebrafish lines carrying mutations in one of their steroid receptor genes. To investigate the activity of the receptors in vivo, specific zebrafish reporter lines have been developed, and transcriptomic studies have been carried out to identify biomarkers for steroid receptor action. In this review, an overview of research on steroid receptors in zebrafish is presented, and it is concluded that further exploitation of the possibilities of the zebrafish model system will contribute significantly to the advancement of steroid receptor research in the next decade.

How calcium makes endocytic receptors attractive

DEFF Research Database (Denmark)

Andersen, Christian B F; Moestrup, Søren K

2014-01-01

of the receptor. Endosomal acidification and calcium efflux lead to the essential ligand-receptor affinity switch and separation. Recent data, including crystal structures of receptor-ligand complexes, now reveal how calcium, in different types of domain scaffolds, functions in a common way as a removable...... 'lynchpin' that stabilizes favorable positioning of ligand-attractive receptor residues. In addition to explaining how calcium depletion can cause ligand-receptor dissociation, the new data add further insight into how acidification contributes to dissociation through structural changes that affect...... the receptor calcium sites....

Radiosequence analysis of the human progestin receptor charged with [3H]promegestone. A comparison with the glucocorticoid receptor

International Nuclear Information System (INIS)

Stroemstedt, P.E.B.; Berkenstam, A.; Joernvall, H.G.; Gustafsson, J.A.; Carlstedt-Duke, J.

1990-01-01

Partially purified preparations of the human progestin receptor and the human and rat glucocorticoid receptor proteins were covalently charged with the synthetic progestin, [ 3 H]promegestone, by photoaffinity labeling. After labeling, the denaturated protein was cleaved and the mixture of peptides subjected to radiosequence analysis as previously described for the rat glucocorticoid receptor protein. The radioactivity labels identified, corresponded to Met-759 and Met-909 after photoaffinity labeling of the human progestin receptor, and Met-622 and Cys-754 after labeling of the rat glucocorticoid receptor. The residues labeled in the glucocorticoid receptor are the same as those previously reported to bind triamcinolone actonide. The corresponding residues were also labeled in the human glucocorticoid receptor. Met-759 of the progestin receptor and Met-622 of the rat glucocorticoid receptor are positioned within a segment with an overall high degree of sequence similarity and are equivalent. However, Met-909 (progestin receptor) and Cys-754 (glucocorticoid receptor) do not occur within equivalent segments of the two proteins. Thus, although the two classes of steroid hormone share a common structure within the A-ring, there are subtle differences in their interaction with the two separate receptor proteins

Toll-like receptors in neonatal sepsis.

LENUS (Irish Health Repository)

O'Hare, Fiona M

2013-06-01

Toll-like receptors are vital transmembrane receptors that initiate the innate immune response to many micro-organisms. The discovery of these receptors has improved our understanding of host-pathogen interactions, and these receptors play an important role in the pathogenesis of multiple neonatal conditions such as sepsis and brain injury. Toll-like receptors, especially TLRs 2 and 4, are associated with necrotizing enterocolitis, periventricular leukomalacia and sepsis.

Labeled receptor ligands for spect

International Nuclear Information System (INIS)

Kung, H.F.

1989-01-01

Receptor specific imaging agents for single photon emission computed tomography (SPECT) can potentially be useful in the understanding of basic biochemistry and pharmacology of receptors. SPECT images may also provide tools for evaluation of density and binding kinetics of a specific receptor, information important for diagnosis and patient management. Basic requirements for receptor imaging agents are: (a) they are labeled with short-lived isotopes, (b) they show high selectivity and specific uptake, (c) they exhibit high target/background ratio, and (d) they can be modeled to obtain quantitative information. Several good examples of CNS receptor specific ligands labeled with I-123 have been developed, including iodoQNB, iodoestrogen iodobenzadiazepine, iodobenazepine, iodobenzamides for muscarinic, estrogen benzadiazepine, D-1 and D-2 dopamine receptors. With the advent of newer and faster SPECT imaging devices, it may be feasible to quantitate the receptor density by in vivo imaging techniques. These new brain imaging agents can provide unique diagnostic information, which may not be available through other imaging modalities, such as CT and MRI

The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets.

Science.gov (United States)

Mizejewski, G J

2015-01-01

Recent studies have demonstrated that the carboxyterminal third domain of alpha-fetoprotein (AFP-CD) binds with various ligands and receptors. Reports within the last decade have established that AFP-CD contains a large fragment of amino acids that interact with several different receptor types. Using computer software specifically designed to identify protein-to-protein interaction at amino acid sequence docking sites, the computer searches identified several types of scavenger-associated receptors and their amino acid sequence locations on the AFP-CD polypeptide chain. The scavenger receptors (SRs) identified were CD36, CD163, Stabilin, SSC5D, SRB1 and SREC; the SR-associated receptors included the mannose, low-density lipoprotein receptors, the asialoglycoprotein receptor, and the receptor for advanced glycation endproducts (RAGE). Interestingly, some SR interaction sites were localized on the AFP-derived Growth Inhibitory Peptide (GIP) segment at amino acids #480-500. Following the detection studies, a structural subdomain analysis of both the receptor and the AFP-CD revealed the presence of epidermal growth factor (EGF) repeats, extracellular matrix-like protein regions, amino acid-rich motifs and dimerization subdomains. For the first time, it was reported that EGF-like sequence repeats were identified on each of the three domains of AFP. Thereafter, the localization of receptors on specific cell types were reviewed and their functions were discussed.

Modulating Estrogen Receptor-related Receptor-α Activity Inhibits Cell Proliferation*

Science.gov (United States)

Bianco, Stéphanie; Lanvin, Olivia; Tribollet, Violaine; Macari, Claire; North, Sophie; Vanacker, Jean-Marc

2009-01-01

High expression of the estrogen receptor-related receptor (ERR)-α in human tumors is correlated to a poor prognosis, suggesting an involvement of the receptor in cell proliferation. In this study, we show that a synthetic compound (XCT790) that modulates the activity of ERRα reduces the proliferation of various cell lines and blocks the G1/S transition of the cell cycle in an ERRα-dependent manner. XCT790 induces, in a p53-independent manner, the expression of the cell cycle inhibitor p21waf/cip1 at the protein, mRNA, and promoter level, leading to an accumulation of hypophosphorylated Rb. Finally, XCT790 reduces cell tumorigenicity in Nude mice. PMID:19546226

Functionally biased signalling properties of 7TM receptors - opportunities for drug development for the ghrelin receptor

DEFF Research Database (Denmark)

Sivertsen, B; Holliday, N; Madsen, A N

2013-01-01

UNLABELLED: The ghrelin receptor is a 7 transmembrane (7TM) receptor involved in a variety of physiological functions including growth hormone secretion, increased food intake and fat accumulation as well as modulation of reward and cognitive functions. Because of its important role in metabolism...... and energy expenditure, the ghrelin receptor has become an important therapeutic target for drug design and the development of anti-obesity compounds. However, none of the compounds developed so far have been approved for commercial use. Interestingly, the ghrelin receptor is able to signal through several...... review, we have described how ligands and mutations in the 7TM receptor may bias the receptors to favour either one G-protein over another or to promote G-protein independent signalling pathways rather than G-protein-dependent pathways. For the ghrelin receptor, both agonist and inverse agonists have...

Ionotropic crustacean olfactory receptors.

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Elizabeth A Corey

Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

Synthèses enzymatiques de néoglucoconjugués catalysées par l'alpha-glucosidase purifiée de la blatte Periplaneta americana (Linnaeus

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Kamenan A.

2005-01-01

Full Text Available Enzymatic synthesis of neoglucoconjugates by purified α-glucosidase from cockroach Periplaneta americana (Linnaeus. Cockroach Periplaneta americana (Linnaeus contains in his digestive tract an acid (pH 5,0 and mesophile (50°C α-glucosidase. This enzyme, purified to homogeneity, hydrolyses highly maltose, sucrose and p-nitrophenyl-α-Dglucopyranoside. The ability of α-glucosidase from cockroach purified to homogeneity to catalyse transglucosylation reactions was tested using maltose and saccharose as glucosyl donors and 2-phenylethanol and phenol as acceptors. The experimental conditions were optimized in relation to the time course of the reaction, pH and concentrations of glucosyl donors and acceptors. The yields in transglucosylation reactions at 37 °C were very high and could attain 67% and 48% with 2-phenylethanol and phenol respectively as glucosyl acceptors. This α-glucosidase hydrolyzed the products formed. It seems that the products formed were the phenylethyl-α-D-glucoside and phenyl-α-D-glucoside. These results suggest that α- glucosidase from cockroach is an exoglucosidase which catalyse the splitting of the α-glucosyl residue from the non reducing terminal of the substrate to liberate α-glucose. This comportment indicates that this enzyme operated by a mechanism involving the retention of the anomeric configuration. On the basis of this work, α-glucosidase from P. americana appears to be a valuable tool for the preparation of α-neoglucoconjugates.

Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling

Science.gov (United States)

Mattila, Pieta K.; Batista, Facundo D.

2016-01-01

Recent evidence implicates the actin cytoskeleton in the control of receptor signaling. This may be of particular importance in the context of immune receptors, such as the B cell receptor, where dysregulated signaling can result in autoimmunity and malignancy. Here, we discuss the role of the actin cytoskeleton in controlling receptor compartmentalization, dynamics, and clustering as a means to regulate receptor signaling through controlling the interactions with protein partners. We propose that the actin cytoskeleton is a point of integration for receptor cross talk through modulation of protein dynamics and clustering. We discuss the implication of this cross talk via the cytoskeleton for both ligand-induced and low-level constitutive (tonic) signaling necessary for immune cell survival. PMID:26833785

DMPD: Toll-like receptor 3: a link between toll-like receptor, interferon and viruses. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 15031527 Toll-like receptor 3: a link between toll-like receptor, interferon and virus... (.csml) Show Toll-like receptor 3: a link between toll-like receptor, interferon and viruses. PubmedID 1503...1527 Title Toll-like receptor 3: a link between toll-like receptor, interferon and virus

Andrographolide regulates epidermal growth factor receptor and transferrin receptor trafficking in epidermoid carcinoma (A-431) cells

Science.gov (United States)

Tan, Y; Chiow, KH; Huang, D; Wong, SH

2010-01-01

Background and purpose: Andrographolide is the active component of Andrographis paniculata, a plant used in both Indian and Chinese traditional medicine, and it has been demonstrated to induce apoptosis in different cancer cell lines. However, not much is known about how it may affect the key receptors implicated in cancer. Knowledge of how andrographolide affects receptor trafficking will allow us to better understand new mechanisms by which andrographolide may cause death in cancer cells. Experimental approach: We utilized the well-characterized epidermal growth factor receptor (EGFR) and transferrin receptor (TfR) expressed in epidermoid carcinoma (A-431) cells as a model to study the effect of andrographolide on receptor trafficking. Receptor distribution, the total number of receptors and surface receptors were analysed by immunofluorescence, Western blot as well as flow-cytometry respectively. Key results: Andrographolide treatment inhibited cell growth, down-regulated EGFRs on the cell surface and affected the degradation of EGFRs and TfRs. The EGFR was internalized into the cell at an increased rate, and accumulated in a compartment that co-localizes with the lysosomal-associated membrane protein in the late endosomes. Conclusion and implications: This study sheds light on how andrographolide may affect receptor trafficking by inhibiting receptor movement from the late endosomes to lysosomes. The down-regulation of EGFR from the cell surface also indicates a new mechanism by which andrographolide may induce cancer cell death. PMID:20233216

In vivo studies of opiate receptors

International Nuclear Information System (INIS)

Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

1984-01-01

To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented

In vivo studies of opiate receptors

Energy Technology Data Exchange (ETDEWEB)

Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

1984-01-01

To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

Differential trafficking of AMPA receptors following activation of NMDA receptors and mGluRs

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Sanderson Thomas M

2011-07-01

Full Text Available Abstract The removal of AMPA receptors from synapses is a major component of long-term depression (LTD. How this occurs, however, is still only partially understood. To investigate the trafficking of AMPA receptors in real-time we previously tagged the GluA2 subunit of AMPA receptors with ecliptic pHluorin and studied the effects of NMDA receptor activation. In the present study we have compared the effect of NMDA receptor and group I mGluR activation, using GluA2 tagged with super ecliptic pHluorin (SEP-GluA2 expressed in cultured hippocampal neurons. Surprisingly, agonists of the two receptors, which are both able to induce chemical forms of LTD, had clearly distinct effects on AMPA receptor trafficking. In agreement with our previous work we found that transient NMDA receptor activation results in an initial decrease in surface GluA2 from extrasynaptic sites followed by a delayed reduction in GluA2 from puncta (putative synapses. In contrast, transient activation of group I mGluRs, using DHPG, led to a pronounced but more delayed decrease in GluA2 from the dendritic shafts. Surprisingly, there was no average change in the fluorescence of the puncta. Examination of fluorescence at individual puncta, however, indicated that alterations did take place, with some puncta showing an increase and others a decrease in fluorescence. The effects of DHPG were, like DHPG-induced LTD, prevented by treatment with a protein tyrosine phosphatase (PTP inhibitor. The electrophysiological correlate of the effects of DHPG in the SEP-GluA2 infected cultures was a reduction in mEPSC frequency with no change in amplitude. The implications of these findings for the initial mechanisms of expression of both NMDA receptor- and mGluR-induced LTD are discussed.

Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat

NARCIS (Netherlands)

Gispen, W.H.; Adan, R.A.H.; Szklarczyk, A.W.; Oosterom, J.; Brakkee, J.H.; Nijenhuis, W.A.; Schaaper, W.M.; Meloen, R.H.

1999-01-01

Since the melanocortin MC3 and melanocortin MC4 receptors are the main melanocortin receptor subtypes expressed in rat brain, we characterized the activity and affinity of nine melanocortin receptor ligands using these receptors in vitro, as well as their activity in a well-defined

A bioluminescence resonance energy transfer 2 (BRET2) assay for monitoring seven transmembrane receptor and insulin receptor crosstalk

DEFF Research Database (Denmark)

Sanni, Samra Joke; Kulahin, Nikolaj; Jorgensen, Rasmus

2017-01-01

The angiotensin AT1 receptor is a seven transmembrane (7TM) receptor, which mediates the regulation of blood pressure. Activation of angiotensin AT1 receptor may lead to impaired insulin signaling indicating crosstalk between angiotensin AT1 receptor and insulin receptor signaling pathways....... To elucidate the molecular mechanisms behind this crosstalk, we applied the BRET2 technique to monitor the effect of angiotensin II on the interaction between Rluc8 tagged insulin receptor and GFP2 tagged insulin receptor substrates 1, 4, 5 (IRS1, IRS4, IRS5) and Src homology 2 domain-containing protein (Shc......). We demonstrate that angiotensin II reduces the interaction between insulin receptor and IRS1 and IRS4, respectively, while the interaction with Shc is unaffected, and this effect is dependent on Gαq activation. Activation of other Gαq-coupled 7TM receptors led to a similar reduction in insulin...

The repertoire of olfactory C family G protein-coupled receptors in zebrafish: candidate chemosensory receptors for amino acids

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Ngai John

2006-12-01

Full Text Available Abstract Background Vertebrate odorant receptors comprise at least three types of G protein-coupled receptors (GPCRs: the OR, V1R, and V2R/V2R-like receptors, the latter group belonging to the C family of GPCRs. These receptor families are thought to receive chemosensory information from a wide spectrum of odorant and pheromonal cues that influence critical animal behaviors such as feeding, reproduction and other social interactions. Results Using genome database mining and other informatics approaches, we identified and characterized the repertoire of 54 intact "V2R-like" olfactory C family GPCRs in the zebrafish. Phylogenetic analysis – which also included a set of 34 C family GPCRs from fugu – places the fish olfactory receptors in three major groups, which are related to but clearly distinct from other C family GPCRs, including the calcium sensing receptor, metabotropic glutamate receptors, GABA-B receptor, T1R taste receptors, and the major group of V2R vomeronasal receptor families. Interestingly, an analysis of sequence conservation and selective pressure in the zebrafish receptors revealed the retention of a conserved sequence motif previously shown to be required for ligand binding in other amino acid receptors. Conclusion Based on our findings, we propose that the repertoire of zebrafish olfactory C family GPCRs has evolved to allow the detection and discrimination of a spectrum of amino acid and/or amino acid-based compounds, which are potent olfactory cues in fish. Furthermore, as the major groups of fish receptors and mammalian V2R receptors appear to have diverged significantly from a common ancestral gene(s, these receptors likely mediate chemosensation of different classes of chemical structures by their respective organisms.

Intracellular insulin-receptor dissociation and segregation in a rat fibroblast cell line transfected with a human insulin receptor gene

International Nuclear Information System (INIS)

Levy, J.R.; Olefsky, J.M.

1988-01-01

The cellular processing of insulin and insulin receptors was studied using a rat fibroblast cell line that had been transfected with a normal human insulin receptor gene, expressing approximately 500 times the normal number of native fibroblasts insulin receptors. These cells bind and internalize insulin normally. Biochemically assays based on the selective precipitation by polyethylene glycol of intact insulin-receptor complexes but not of free intracellular insulin were developed to study the time course of intracellular insulin-receptor dissociation. Fibroblasts were incubated with radiolabeled insulin at 4 0 C, and internalization of insulin-receptor complexes was initiated by warming the cells to 37 0 C. Within 2 min, 90% of the internalized radioactivity was composed of intact insulin-receptor complexes. The dissociation of insulin from internalized insulin-receptor complexes was markedly inhibited by monensin and chloroquine. Furthermore, chloroquine markedly increased the number of cross-linkable intracellular insulin-receptor complexes, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiography. These findings suggest that acidification of intracellular vesicles is responsible for insulin-receptor dissociation. Physical segregation of dissociated intracellular insulin from its receptor was monitored. The results are consistent with the view that segregation of insulin and receptor occurs 5-10 min after initiation of dissociation. These studies demonstrate the intracellular itinerary of insulin-receptor complexes, including internalization, dissociation of insulin from the internalized receptor within an acidified compartment, segregation of insulin from the receptor, and subsequent ligand degradation

Functional ET(A)-ET(B) Receptor Cross-talk in Basilar Artery In Situ From ET(B) Receptor Deficient Rats.

Science.gov (United States)

Yoon, SeongHun; Gariepy, Cheryl E; Yanagisawa, Masashi; Zuccarello, Mario; Rapoport, Robert M

2016-03-01

The role of endothelin (ET)(A)-ET(B) receptor cross-talk in limiting the ET(A) receptor antagonist inhibition of ET-1 constriction is revealed by the partial or complete dependency of the ET(A) receptor antagonist inhibition on functional removal of the ET(B) receptor. Although functional removal of the ET(B) receptor is generally accomplished with ET(B) receptor antagonist, a novel approach using rats containing a naturally occurring deletion mutation in the ET(B) receptor [rescued "spotting lethal" (sl) rats; ET(B)(sl/sl)] demonstrated increased ET(A) receptor antagonist inhibition of ET-1 constriction in vena cava. We investigated whether this deletion mutation was also sufficient to remove the ET(B) receptor dependency of the ET(A) receptor antagonist inhibition of ET-1 constriction in the basilar artery. Consistent with previous reports, ET-1 plasma levels were elevated in ET(B)(sl/sl) as compared with ET(B)(+/+) rats. ET(B) receptor antagonist failed to relax the ET-1 constricted basilar artery from ET(B)(+/+) and ET(B)(sl/sl) rats. Relaxation to combined ET(A) and ET(B) receptor antagonist was greater than relaxation to ET(A) receptor antagonist in the basilar artery from ET(B)(+/+) and, unexpectedly, ET(B)(sl/sl) rats. These findings confirm the presence of ET(A)-ET(B) receptor cross-talk in the basilar artery. We speculate that mutant ET(B) receptor expression produced by alternative splicing may be sufficient to allow cross-talk.

Subtype selective kainic acid receptor agonists

DEFF Research Database (Denmark)

Bunch, Lennart; Krogsgaard-Larsen, Povl

2009-01-01

(S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

Hypoxia increases pulmonary arterial thromboxane receptor internalization independent of receptor sensitization.

Science.gov (United States)

Fediuk, J; Sikarwar, A S; Lizotte, P P; Hinton, M; Nolette, N; Dakshinamurti, S

2015-02-01

Persistent Pulmonary Hypertension of the Newborn (PPHN) is characterized by sustained vasospasm and an increased thromboxane:prostacyclin ratio. Thromboxane (TP) receptors signal via Gαq to mobilize IP3 and Ca(2+), causing pulmonary arterial constriction. We have previously reported increased TP internalization in hypoxic pulmonary arterial (PA) myocytes. Serum-deprived PA myocytes were grown in normoxia (NM) or hypoxia (HM) for 72 h. TP localization was visualized in agonist-naïve and -challenged NM and HM by immunocytochemistry. Pathways for agonist-induced TP receptor internalization were determined by inhibiting caveolin- or clathrin-mediated endocytosis, and caveolar fractionation. Roles of actin and tubulin in TP receptor internalization were assessed using inhibitors of tubulin, actin-stabilizing or -destabilizing agents. PKA, PKC or GRK activation and inhibition were used to determine the kinase responsible for post-agonist receptor internalization. Agonist-naïve HM had decreased cell surface TP, and greater TP internalization after agonist challenge. TP protein did not sort with caveolin-rich fractions. Inhibition of clathrin prevented TP internalization. Both actin-stabilizing and -destabilizing agents prevented TP endocytosis in NM, while normalizing TP internalization in HM. Velocity of TP internalization was unaffected by PKA activity, but PKC activation normalized TP receptor internalization in HM. GRK inhibition had no effect. We conclude that in hypoxic myocytes, TP is internalized faster and to a greater extent than in normoxic controls. Internalization of the agonist-challenged TP requires clathrin, dynamic actin and is sensitive to PKC activity. TP receptor trafficking and signaling in hypoxia are pivotal to understanding increased vasoconstrictor sensitivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Toll-like receptor 2 or toll-like receptor 4 deficiency does not modify lupus in MRLlpr mice.

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Simon J Freeley

Full Text Available Systemic lupus erythematosus is an autoimmune disease with a high morbidity and nephritis is a common manifestation. Previous studies in murine lupus models have suggest a role for Toll-like receptor 2 and 4. We examined the role of these molecules in MRL lpr mice which is one of the most established and robust murine models. We compared disease parameters in Toll-like receptor 2 or Toll-like receptor 4 deficient mice with their littermate controls. We found no difference in the severity of glomerulonephritis as assessed by histology, serum creatinine and albuminuria when Toll-like receptor 2 or Toll-like receptor 4 deficient MRLlpr mice were compared with Toll-like receptor sufficient controls. We also found similar levels of anti-dsDNA and anti-ssDNA antibodies. These results show that Toll-like receptor 2 and Toll-like receptor 4 do not play a significant role in MRLlpr mice, and therefore they may not be important in human lupus.

Involvement of direct inhibition of NMDA receptors in the effects of sigma-receptor ligands on glutamate neurotoxicity in vitro.

Science.gov (United States)

Nishikawa, H; Hashino, A; Kume, T; Katsuki, H; Kaneko, S; Akaike, A

2000-09-15

This study was performed to examine the roles of the N-methyl-D-aspartate (NMDA) receptor/phencyclidine (PCP) channel complex in the protective effects of sigma-receptor ligands against glutamate neurotoxicity in cultured cortical neurons derived from fetal rats. A 1-h exposure of cultures to glutamate caused a marked loss of viability, as determined by Trypan blue exclusion. This acute neurotoxicity of glutamate was prevented by NMDA receptor antagonists. Expression of sigma(1) receptor mRNA in cortical cultures was confirmed by reverse transcription polymerase chain reaction (RT-PCR). sigma Receptor ligands with affinity for NMDA receptor channels including the PCP site, such as (+)-N-allylnormetazocine ((+)-SKF10,047), haloperidol, and R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane ((-)-PPAP), prevented glutamate neurotoxicity in a concentration-dependent manner. In contrast, other sigma-receptor ligands without affinity for NMDA receptors, such as carbetapentane and R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine ((+)-3-PPP), did not show neuroprotective effects. Putative endogenous sigma receptor ligands such as pregnenolone, progesterone, and dehydroepiandrosterone did not affect glutamate neurotoxicity. The protective effects of (+)-SKF10,047, haloperidol, and (-)-PPAP were not affected by the sigma(1) receptor antagonist rimcazole. These results suggested that a direct interaction with NMDA receptors but not with sigma receptors plays a crucial role in the neuroprotective effects of sigma receptor ligands with affinity for NMDA receptors.

β1-adrenergic receptor stimulation by agonist Compound 49b restores insulin receptor signal transduction in vivo

Science.gov (United States)

Jiang, Youde; Zhang, Qiuhua; Ye, Eun-Ah

2014-01-01

Purpose Determine whether Compound 49b treatment ameliorates retinal changes due to the lack of β2-adrenergic receptor signaling. Methods Using retinas from 3-month-old β2-adrenergic receptor-deficient mice, we treated mice with our novel β1-/β2-adrenergic receptor agonist, Compound 49b, to assess the effects of adrenergic agonists acting only on β1-adrenergic receptors due to the absence of β2-adrenergic receptors. Western blotting or enzyme-linked immunosorbent assay (ELISA) analyses were performed for β1- and β2-adrenergic receptors, as well as key insulin resistance proteins, including TNF-α, SOCS3, IRS-1Ser307, and IRTyr960. Analyses were also performed on key anti- and proapoptotic proteins: Akt, Bcl-xL, Bax, and caspase 3. Electroretinogram analyses were conducted to assess functional changes, while histological assessment was conducted for changes in retinal thickness. Results A 2-month treatment of β2-adrenergic receptor-deficient mice with daily eye drops of 1 mM Compound 49b, a novel β1- and β2-adrenergic receptor agonist, reversed the changes in insulin resistance markers (TNF-α and SOCS3) observed in untreated β2-adrenergic receptor-deficient mice, and concomitantly increased morphological integrity (retinal thickness) and functional responses (electroretinogram amplitude). These results suggest that stimulating β1-adrenergic receptors on retinal endothelial cells or Müller cells can compensate for the loss of β2-adrenergic receptor signaling on Müller cells, restore insulin signal transduction, reduce retinal apoptosis, and enhance retinal function. Conclusions Since our previous studies with β1-adrenergic receptor knockout mice confirmed that the reverse also occurs (β2-adrenergic receptor stimulation can compensate for the loss of β1-adrenergic receptor activity), it appears that increased activity in either of these pathways alone is sufficient to block insulin resistance–based retinal cell apoptosis. PMID:24966659

Protein Connectivity in Chemotaxis Receptor Complexes.

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Stephan Eismann

2015-12-01

Full Text Available The chemotaxis sensory system allows bacteria such as Escherichia coli to swim towards nutrients and away from repellents. The underlying pathway is remarkably sensitive in detecting chemical gradients over a wide range of ambient concentrations. Interactions among receptors, which are predominantly clustered at the cell poles, are crucial to this sensitivity. Although it has been suggested that the kinase CheA and the adapter protein CheW are integral for receptor connectivity, the exact coupling mechanism remains unclear. Here, we present a statistical-mechanics approach to model the receptor linkage mechanism itself, building on nanodisc and electron cryotomography experiments. Specifically, we investigate how the sensing behavior of mixed receptor clusters is affected by variations in the expression levels of CheA and CheW at a constant receptor density in the membrane. Our model compares favorably with dose-response curves from in vivo Förster resonance energy transfer (FRET measurements, demonstrating that the receptor-methylation level has only minor effects on receptor cooperativity. Importantly, our model provides an explanation for the non-intuitive conclusion that the receptor cooperativity decreases with increasing levels of CheA, a core signaling protein associated with the receptors, whereas the receptor cooperativity increases with increasing levels of CheW, a key adapter protein. Finally, we propose an evolutionary advantage as explanation for the recently suggested CheW-only linker structures.

Structural Insights into Selective Ligand-Receptor Interactions Leading to Receptor Inactivation Utilizing Selective Melanocortin 3 Receptor Antagonists.

Science.gov (United States)

Cai, Minying; Marelli, Udaya Kiran; Mertz, Blake; Beck, Johannes G; Opperer, Florian; Rechenmacher, Florian; Kessler, Horst; Hruby, Victor J

2017-08-15

Systematic N-methylated derivatives of the melanocortin receptor ligand, SHU9119, lead to multiple binding and functional selectivity toward melanocortin receptors. However, the relationship between N-methylation-induced conformational changes in the peptide backbone and side chains and melanocortin receptor selectivity is still unknown. We conducted comprehensive conformational studies in solution of two selective antagonists of the third isoform of the melanocortin receptor (hMC3R), namely, Ac-Nle-c[Asp-NMe-His 6 -d-Nal(2') 7 -NMe-Arg 8 -Trp 9 -Lys]-NH 2 (15) and Ac-Nle-c[Asp-His 6 -d-Nal(2') 7 -NMe-Arg 8 -NMe-Trp 9 -NMe-Lys]-NH 2 (17). It is known that the pharmacophore (His 6 -DNal 7 -Arg 8 -Trp 9 ) of the SHU-9119 peptides occupies a β II-turn-like region with the turn centered about DNal 7 -Arg 8 . The analogues with hMC3R selectivity showed distinct differences in the spatial arrangement of the Trp 9 side chains. In addition to our NMR studies, we also carried out molecular-level interaction studies of these two peptides at the homology model of hMC3R. Earlier chimeric human melanocortin 3 receptor studies revealed insights regarding the binding and functional sites of hMC3R selectivity. Upon docking of peptides 15 and 17 to the binding pocket of hMC3R, it was revealed that Arg 8 and Trp 9 side chains are involved in a majority of the interactions with the receptor. While Arg 8 forms polar contacts with D154 and D158 of hMC3R, Trp 9 utilizes π-π stacking interactions with F295 and F298, located on the transmembrane domain of hMC3R. It is hypothesized that as the frequency of Trp 9 -hMC3R interactions decrease, antagonistic activity increases. The absence of any interactions of the N-methyl groups with hMC3R suggests that their primary function is to modulate backbone conformations of the ligands.

Constitutive dimerization of the G-protein coupled receptor, neurotensin receptor 1, reconstituted into phospholipid bilayers.

Science.gov (United States)

Harding, Peter J; Attrill, Helen; Boehringer, Jonas; Ross, Simon; Wadhams, George H; Smith, Eleanor; Armitage, Judith P; Watts, Anthony

2009-02-01

Neurotensin receptor 1 (NTS1), a Family A G-protein coupled receptor (GPCR), was expressed in Escherichia coli as a fusion with the fluorescent proteins eCFP or eYFP. A fluorophore-tagged receptor was used to study the multimerization of NTS1 in detergent solution and in brain polar lipid bilayers, using fluorescence resonance energy transfer (FRET). A detergent-solubilized receptor was unable to form FRET-competent complexes at concentrations of up to 200 nM, suggesting that the receptor is monomeric in this environment. When reconstituted into a model membrane system at low receptor density, the observed FRET was independent of agonist binding, suggesting constitutive multimer formation. In competition studies, decreased FRET in the presence of untagged NTS1 excludes the possibility of fluorescent protein-induced interactions. A simulation of the experimental data indicates that NTS1 exists predominantly as a homodimer, rather than as higher-order multimers. These observations suggest that, in common with several other Family A GPCRs, NTS1 forms a constitutive dimer in lipid bilayers, stabilized through receptor-receptor interactions in the absence of other cellular signaling components. Therefore, this work demonstrates that well-characterized model membrane systems are useful tools for the study of GPCR multimerization, allowing fine control over system composition and complexity, provided that rigorous control experiments are performed.

Interaction of chemokines with their receptors--from initial chemokine binding to receptor activating steps

DEFF Research Database (Denmark)

Thiele, Stefanie; Rosenkilde, Mette Marie

2014-01-01

and surveillance. Chemokines are a group of 8-12 kDa large peptides with a secondary structure consisting of a flexible N-terminus and a core-domain usually stabilized by two conserved disulfide bridges. They mainly interact with the extracellular domains of their cognate 7TM receptors. Affinityand activity......-contributing interactions are attributed to different domains and known to occur in two steps. Here, knowledge on chemokine and receptor domains involved in the first binding-step and the second activation-step is reviewed. A mechanism comprising at least two steps seems consistent; however, several intermediate...... interactions possibly occur, resulting in a multi-step process, as recently proposed for other 7TM receptors. Overall, the N-terminus of chemokine receptors is pivotal for binding of all chemokines. During receptor activation, differences between the two major chemokine subgroups occur, as CC-chemokines mainly...

Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor

Energy Technology Data Exchange (ETDEWEB)

Wu, Kailang; Li, Weikai; Peng, Guiqing; Li, Fang; (Harvard-Med); (UMM-MED)

2010-03-04

NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel {beta}-sandwich core structure consisting of 2 layers of {beta}-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homology in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a 'virus-binding hotspot' on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus-receptor interactions.

Fibroblast growth factor receptors in breast cancer.

Science.gov (United States)

Wang, Shuwei; Ding, Zhongyang

2017-05-01

Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of breast cancer. Recent genetic studies have identified some subtypes of fibroblast growth factor receptors as strong genetic loci associated with breast cancer. In this article, we review the recent epidemiological findings and experiment results of fibroblast growth factor receptors in breast cancer. First, we summarized the structure and physiological function of fibroblast growth factor receptors in humans. Then, we discussed the common genetic variations in fibroblast growth factor receptors that affect breast cancer risk. In addition, we also introduced the potential roles of each fibroblast growth factor receptors isoform in breast cancer. Finally, we explored the potential therapeutics targeting fibroblast growth factor receptors for breast cancer. Based on the biological mechanisms of fibroblast growth factor receptors leading to the pathogenesis in breast cancer, targeting fibroblast growth factor receptors may provide new opportunities for breast cancer therapeutic strategies.

Sigma opioid receptor: characterization and co-identity with the phencyclidine receptor

International Nuclear Information System (INIS)

Mendelsohn, L.G.; Kalra, V.; Johnson, B.G.; Kerchner, G.A.

1985-01-01

The properties of the sigma opioid receptor of rat brain cortex have been characterized using the prototypic ligand (+)-[ 3 H] SKF 10,047. Binding to this receptor was rapid, and equilibrium was obtained within 30 min at 37 degrees C. Specific binding was linear with protein concentration up to 500 micrograms/2 ml and was dependent upon protein integrity. Denaturation by boiling destroyed over 95% of the specific binding. A high-affinity binding site with a KD of 150 +/- 40 nM and a maximum binding of 2.91 +/- 0.84 pmol/mg of protein was determined from a Scatchard plot of the binding data. The addition of salt, either NaCl or CaCl 2 , to the buffers markedly decreased binding, with CaCl 2 being more potent than NaCl. A broad pH optimum for specific binding was observed; maximum binding was at pH 9.0. The affinity of a number of ligands for the sigma site and the phencyclidine receptor were compared. The binding (IC50) of 13 ligands to the sigma site showed a correlation of 0.86 (P less than .01) with binding to the phencyclidine site. The data demonstrate that the biochemical properties of the sigma and phencyclidine receptors are similar and support the view that these receptors are one and the same site

Adenosine Receptors and Wound Healing

Directory of Open Access Journals (Sweden)

Bruce N. Cronstein

2004-01-01

Full Text Available Recent studies have demonstrated that application of topical adenosine A2A receptor agonists promotes more rapid wound closure and clinical studies are currently underway to determine the utility of topical A2A adenosine receptor agonists in the therapy of diabetic foot ulcers. The effects of adenosine A2A receptors on the cells and tissues of healing wounds have only recently been explored. We review here the known effects of adenosine A2A receptor occupancy on the cells involved in wound healing.

Receptor-targeted metalloradiopharmaceuticals. Final technical report

International Nuclear Information System (INIS)

Green, Mark A.

2000-01-01

Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy

Rat hepatic β2-adrenergic receptor: structural similarities to the rat fat cell β1-adrenergic receptor

International Nuclear Information System (INIS)

Graziano, M.P.

1984-01-01

The mammalian β 2 -adrenergic receptor from rat liver has been purified by sequential cycles of affinity chromatography followed by steric-exclusion high performance liquid chromatography. Electrophoresis of highly purified receptor preparations on polyacrylamide gels in the presence of sodium dodecyl sulfate under reducing conditions reveals a single peptide M/sub r/ = 67,000, as judged by silver staining. Purified β 2 -adrenergic receptor migrates on steric-exclusion high performance liquid chromatography in two peaks, with M/sub r/ = 140,000 and 67,000. Specific binding of the high affinity, β-adrenergic receptor antagonists (-)[ 3 H]dihydroalprenolol and (-)[ 125 I]iodocyanopindolol to purified rat liver β-adrenergic receptor preparations displays stereoselectivity for (-)isomers of agonists and a rank order of potencies for agonists characteristics of a β 2 -adrenergic receptor. Radioiodinated, β 1 -adrenergic receptors from rat fat cells and β 2 -adrenergic receptors from rat liver purified in the presence of protease inhibitors comigrate in electrophoretic separations on polyacrylamide gels in the presence of sodium dodecyl sulfate as 67,000-M/sub r/ peptides. Autoradiograms of two dimensional partial proteolytic digests of the purified, radioiodinated rat liver β 2 -adrenergic receptor, generated with α-chymotrypsin, S. aureus V8 protease and elastase reveal a pattern of peptide fragments essentially identical to those generated by partial proteolytic digests of the purified, radioiodinated β 1 -adrenergic receptor from rat fat cells, by these same proteases. These data indicate that a high degree of homology exists between these two pharmacologically distinct mammalian β-adrenergic receptor proteins

Manipulation of Very Few Receptor Discriminator Residues Greatly Enhances Receptor Specificity of Non-visual Arrestins*

Science.gov (United States)

Gimenez, Luis E.; Vishnivetskiy, Sergey A.; Baameur, Faiza; Gurevich, Vsevolod V.

2012-01-01

Based on the identification of residues that determine receptor selectivity of arrestins and the analysis of the evolution in the arrestin family, we introduced 10 mutations of “receptor discriminator” residues in arrestin-3. The recruitment of these mutants to M2 muscarinic (M2R), D1 (D1R) and D2 (D2R) dopamine, and β2-adrenergic receptors (β2AR) was assessed using bioluminescence resonance energy transfer-based assays in cells. Seven of 10 mutations differentially affected arrestin-3 binding to individual receptors. D260K and Q262P reduced the binding to β2AR, much more than to other receptors. The combination D260K/Q262P virtually eliminated β2AR binding while preserving the interactions with M2R, D1R, and D2R. Conversely, Y239T enhanced arrestin-3 binding to β2AR and reduced the binding to M2R, D1R, and D2R, whereas Q256Y selectively reduced recruitment to D2R. The Y239T/Q256Y combination virtually eliminated the binding to D2R and reduced the binding to β2AR and M2R, yielding a mutant with high selectivity for D1R. Eleven of 12 mutations significantly changed the binding to light-activated phosphorhodopsin. Thus, manipulation of key residues on the receptor-binding surface modifies receptor preference, enabling the construction of non-visual arrestins specific for particular receptor subtypes. These findings pave the way to the construction of signaling-biased arrestins targeting the receptor of choice for research or therapeutic purposes. PMID:22787152

Manipulation of very few receptor discriminator residues greatly enhances receptor specificity of non-visual arrestins.

Science.gov (United States)

Gimenez, Luis E; Vishnivetskiy, Sergey A; Baameur, Faiza; Gurevich, Vsevolod V

2012-08-24

Based on the identification of residues that determine receptor selectivity of arrestins and the analysis of the evolution in the arrestin family, we introduced 10 mutations of "receptor discriminator" residues in arrestin-3. The recruitment of these mutants to M2 muscarinic (M2R), D1 (D1R) and D2 (D2R) dopamine, and β(2)-adrenergic receptors (β(2)AR) was assessed using bioluminescence resonance energy transfer-based assays in cells. Seven of 10 mutations differentially affected arrestin-3 binding to individual receptors. D260K and Q262P reduced the binding to β(2)AR, much more than to other receptors. The combination D260K/Q262P virtually eliminated β(2)AR binding while preserving the interactions with M2R, D1R, and D2R. Conversely, Y239T enhanced arrestin-3 binding to β(2)AR and reduced the binding to M2R, D1R, and D2R, whereas Q256Y selectively reduced recruitment to D2R. The Y239T/Q256Y combination virtually eliminated the binding to D2R and reduced the binding to β(2)AR and M2R, yielding a mutant with high selectivity for D1R. Eleven of 12 mutations significantly changed the binding to light-activated phosphorhodopsin. Thus, manipulation of key residues on the receptor-binding surface modifies receptor preference, enabling the construction of non-visual arrestins specific for particular receptor subtypes. These findings pave the way to the construction of signaling-biased arrestins targeting the receptor of choice for research or therapeutic purposes.

Laminar pattern of cholinergic and adrenergic receptors in rat visual cortex using quantitative receptor autoradiography

International Nuclear Information System (INIS)

Schliebs, R.; Walch, C.

1989-01-01

The laminar distribution of muscarinic acetylcholine receptors, including the M1-receptor subtype, of beta-adrenergic receptors, and noradrenaline uptake sites, was studied in the adult rat visual, frontal, somatosensory and motor cortex, using quantitative receptor autoradiography. In the visual cortex, the highest density of muscarinic acetylcholine receptors was found in layer I. From layer II/III to layer V binding decreases continueously reaching a constant binding level in layers V and VI. This laminar pattern of muscarinic receptor density differs somewhat from that observed in the non-visual cortical regions examined: layer II/III contained the highest receptor density followed by layer I and IV: lowest density was found in layer V and VI. The binding profile of the muscarinic cholinergic M1-subtype through the visual cortex shows a peak in cortical layer II and in the upper part of layer VI, whereas in the non-visual cortical regions cited the binding level was high in layer II/III, moderate in layer I and IV, and low in layer VI. Layers I to IV of the visual cortex contained the highest beta-adrenergic receptor densities, whereas only low binding levels were observed in the deeper layers. A similar laminar distribution was found also in the frontal, somatosensory and motor cortex. The density of noradrenaline uptake sites was high in all layers of the cortical regions studied, but with noradrenaline uptake sites somewhat more concentrated in the superficial layers than in deeper ones. The distinct laminar pattern of cholinergic and noradrenergic receptor sites indicates a different role for acetylcholine and noradrenaline in the functional anatomy of the cerebral cortex, and in particular, the visual cortex. (author)

Laminar pattern of cholinergic and adrenergic receptors in rat visual cortex using quantitative receptor autoradiography

Energy Technology Data Exchange (ETDEWEB)

Schliebs, R; Walch, C [Leipzig Univ. (German Democratic Republic). Bereich Medizin; Stewart, M G [Open Univ., Milton Keynes (UK)

1989-01-01

The laminar distribution of muscarinic acetylcholine receptors, including the M1-receptor subtype, of beta-adrenergic receptors, and noradrenaline uptake sites, was studied in the adult rat visual, frontal, somatosensory and motor cortex, using quantitative receptor autoradiography. In the visual cortex, the highest density of muscarinic acetylcholine receptors was found in layer I. From layer II/III to layer V binding decreases continueously reaching a constant binding level in layers V and VI. This laminar pattern of muscarinic receptor density differs somewhat from that observed in the non-visual cortical regions examined: layer II/III contained the highest receptor density followed by layer I and IV: lowest density was found in layer V and VI. The binding profile of the muscarinic cholinergic M1-subtype through the visual cortex shows a peak in cortical layer II and in the upper part of layer VI, whereas in the non-visual cortical regions cited the binding level was high in layer II/III, moderate in layer I and IV, and low in layer VI. Layers I to IV of the visual cortex contained the highest beta-adrenergic receptor densities, whereas only low binding levels were observed in the deeper layers. A similar laminar distribution was found also in the frontal, somatosensory and motor cortex. The density of noradrenaline uptake sites was high in all layers of the cortical regions studied, but with noradrenaline uptake sites somewhat more concentrated in the superficial layers than in deeper ones. The distinct laminar pattern of cholinergic and noradrenergic receptor sites indicates a different role for acetylcholine and noradrenaline in the functional anatomy of the cerebral cortex, and in particular, the visual cortex. (author).

Radioiodinated ligands for dopamine receptors

International Nuclear Information System (INIS)

Kung, H.F.

1994-01-01

The dopamine receptor system is important for normal brain function; it is also the apparent action site for various neuroleptic drugs for the treatment of schizophrenia and other metal disorders. In the past few years radioiodinated ligands for single photon emission tomography (SPECT) have been successfully developed and tested in humans: [ 123 I]TISCH for D1 dopamine receptors; [ 123 I]IBZM, epidepride, IBF and FIDA2, four iodobenzamide derivatives, for D2/D3 dopamine receptors. In addition, [ 123 I]β-CIT (RTI-55) and IPT, cocaine derivatives, for the dopamine reuptake site are potentially useful for diagnosis of loss of dopamine neurons. The first iodinated ligand, (R)trans-7-OH-PIPAT, for D3 dopamine receptors, was synthesized and characterized with cloned cell lines (Spodoptera frugiperda, Sf9) expressing the D2 and D3 dopamine receptors and with rat basal forebrain membrane preparations. Most of the known iodobenzamides displayed similar potency in binding to both D2 and D3 dopamine receptors expressed in the cell lines. Initial studies appear to suggest that by fine tuning the structures it may be possible to develop agents specific for D2 and D3 dopamine receptors. It is important to investigate D2/D3 selectivity for this series of potent ligands

Prolactin receptor, growth hormone receptor, and putative somatolactin receptor in Mozambique tilapia: tissue specific expression and differential regulation by salinity and fasting.

Science.gov (United States)

Pierce, A L; Fox, B K; Davis, L K; Visitacion, N; Kitahashi, T; Hirano, T; Grau, E G

2007-01-01

In fish, pituitary growth hormone family peptide hormones (growth hormone, GH; prolactin, PRL; somatolactin, SL) regulate essential physiological functions including osmoregulation, growth, and metabolism. Teleost GH family hormones have both differential and overlapping effects, which are mediated by plasma membrane receptors. A PRL receptor (PRLR) and two putative GH receptors (GHR1 and GHR2) have been identified in several teleost species. Recent phylogenetic analyses and binding studies suggest that GHR1 is a receptor for SL. However, no studies have compared the tissue distribution and physiological regulation of all three receptors. We sequenced GHR2 from the liver of the Mozambique tilapia (Oreochromis mossambicus), developed quantitative real-time PCR assays for the three receptors, and assessed their tissue distribution and regulation by salinity and fasting. PRLR was highly expressed in the gill, kidney, and intestine, consistent with the osmoregulatory functions of PRL. PRLR expression was very low in the liver. GHR2 was most highly expressed in the muscle, followed by heart, testis, and liver, consistent with this being a GH receptor with functions in growth and metabolism. GHR1 was most highly expressed in fat, liver, and muscle, suggesting a metabolic function. GHR1 expression was also high in skin, consistent with a function of SL in chromatophore regulation. These findings support the hypothesis that GHR1 is a receptor for SL. In a comparison of freshwater (FW)- and seawater (SW)-adapted tilapia, plasma PRL was strongly elevated in FW, whereas plasma GH was slightly elevated in SW. PRLR expression was reduced in the gill in SW, consistent with PRL's function in freshwater adaptation. GHR2 was elevated in the kidney in FW, and correlated negatively with plasma GH, whereas GHR1 was elevated in the gill in SW. Plasma IGF-I, but not GH, was reduced by 4 weeks of fasting. Transcript levels of GHR1 and GHR2 were elevated by fasting in the muscle. However

Hormonal control of spermatogenesis: expression of FSJH receptor and androgen receptor genes

NARCIS (Netherlands)

L.J. Blok (Leen)

1992-01-01

textabstractFSH and testosterone are the main hormonal regulators of spermatogenesis. The actions of androgens and FSH are mediated by their respective receptors. Receptor gene expression (mRNA and protein). is an important determinant of hormone action. Biochemical aspects of the regulation of

Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2 receptors

International Nuclear Information System (INIS)

Pazos, A.; Cortes, R.; Palacios, J.M.

1985-01-01

The distribution of serotonin-2 (5-HT 2 ) receptors in the rat brain was studied by light microscopic quantitative autoradiography. Receptors were labeled with four ligands: [ 3 H]ketanserin, [ 3 H]mesulergine, [ 3 H]LSD and [ 3 H]spiperone, which are reported to show high affinity for 5-HT 2 receptors. Very high concentrations were localized in the claustrum, olfactory tubercle and layer IV of the neocortex. The anterior olfactory nucleus, piriform cortex and layer I of neocortex were also rich in 5-HT 2 receptors. The specificity of the different ligands used is discussed in terms of the other populations of sites recognized by them. The distribution of 5-HT 2 receptors here reported is discussed in correlation with (a) the known distribution of serotoninergic terminals, (b) the specific anatomical systems and (c) the central effects reported to be mediated by 5-HT 2 -selective drugs. (Auth.)

Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors

International Nuclear Information System (INIS)

Von Schrenck, T.; Heinz-Erian, P.; Moran, T.; Mantey, S.A.; Gardner, J.D.; Jensen, R.T.

1989-01-01

To identify receptors for bombesin-related peptides in the rat esophagus, we measured binding of 125I-Bolton-Hunter neuromedin B (125I-BH-neuromedin B) and 125I-[Tyr4]bombesin to tissue sections from the rat esophagus and compared the results with those for rat pancreas. Esophagus bound both tracers, whereas pancreas bound only 125I-[Tyr4]bombesin. In each tissue binding was saturable, dependent on pH, on time, and on temperature, reversible, and specific. Autoradiography demonstrated binding of both tracers only to the muscularis mucosae of the esophagus and binding of 125I-[Tyr4]bombesin diffusely over pancreatic acini. In the esophagus, the relative potencies for inhibition of binding of both tracers were as follows: neuromedin B greater than bombesin greater than GRP = neuromedin C; similar relative potencies were found for causing contraction of muscle strips from whole esophagus and from the isolated muscularis mucosae. In pancreas tissue sections and dispersed acini, the relative potencies for inhibition of binding of 125I-[Tyr4]bombesin were as follows: bombesin greater than GRP = neuromedin C much greater than neuromedin B. Similar relative potencies were found for stimulation of enzyme secretion from dispersed pancreatic acini. Computer analysis in both tissues demonstrated only a single binding site. The present study demonstrates that rat esophagus muscle possesses specific receptors for bombesin-related peptides. Furthermore, this study shows that the esophageal bombesin receptors represent a previously unidentified class of bombesin receptors in that they have a higher affinity for neuromedin B than for bombesin. In contrast, the pancreatic bombesin receptors have, like all other bombesin receptors described to date, a high affinity for bombesin, but low affinity for neuromedin B

Pharmacological significance of the interplay between angiotensin receptors: MAS receptors as putative final mediators of the effects elicited by angiotensin AT1 receptors antagonists.

Science.gov (United States)

Pernomian, Larissa; Pernomian, Laena; Gomes, Mayara S; da Silva, Carlos H T P

2015-12-15

The interplay between angiotensin AT1 receptors and MAS receptors relies on several inward regulatory mechanisms from renin-angiotensin system (RAS) including the functional crosstalk between angiotensin II and angiotensin-(1-7), the competitive AT1 antagonism exhibited by angiotensin-(1-7), the antagonist feature assigned to AT1/MAS heterodimerization on AT1 signaling and the AT1-mediated downregulation of angiotensin-converting enzyme 2 (ACE2). Recently, such interplay has acquired an important significance to RAS Pharmacology since a few studies have supporting strong evidences that MAS receptors mediate the effects elicited by AT1 antagonists. The present Perspective provides an overview of the regulatory mechanisms involving AT1 and MAS receptors, their significance to RAS Pharmacology and the future directions on the interplay between angiotensin receptors. Copyright © 2015 Elsevier B.V. All rights reserved.

The importance of the adenosine A(2A) receptor-dopamine D(2) receptor interaction in drug addiction.

Science.gov (United States)

Filip, M; Zaniewska, M; Frankowska, M; Wydra, K; Fuxe, K

2012-01-01

Drug addiction is a serious brain disorder with somatic, psychological, psychiatric, socio-economic and legal implications in the developed world. Illegal (e.g., psychostimulants, opioids, cannabinoids) and legal (alcohol, nicotine) drugs of abuse create a complex behavioral pattern composed of drug intake, withdrawal, seeking and relapse. One of the hallmarks of drugs that are abused by humans is that they have different mechanisms of action to increase dopamine (DA) neurotransmission within the mesolimbic circuitry of the brain and indirectly activate DA receptors. Among the DA receptors, D(2) receptors are linked to drug abuse and addiction because their function has been proven to be correlated with drug reinforcement and relapses. The recognition that D(2) receptors exist not only as homomers but also can form heteromers, such as with the adenosine (A)(2A) receptor, that are pharmacologically and functionally distinct from their constituent receptors, has significantly expanded the range of potential drug targets and provided new avenues for drug design in the search for novel drug addiction therapies. The aim of this review is to bring current focus on A(2A) receptors, their physiology and pharmacology in the central nervous system, and to discuss the therapeutic relevance of these receptors to drug addiction. We concentrate on the contribution of A(2A) receptors to the effects of different classes of drugs of abuse examined in preclinical behavioral experiments carried out with pharmacological and genetic tools. The consequences of chronic drug treatment on A(2A) receptor-assigned functions in preclinical studies are also presented. Finally, the neurochemical mechanism of the interaction between A(2A) receptors and drugs of abuse in the context of the heteromeric A(2A)-D(2) receptor complex is discussed. Taken together, a significant amount of experimental analyses provide evidence that targeting A(2A) receptors may offer innovative translational strategies

Characterization of astrocytic and neuronal benzodiazepine receptors

Energy Technology Data Exchange (ETDEWEB)

Bender, A.S.

1988-01-01

Primary cultures of astrocytes and neurons express benzodiazepine receptors. Neuronal benzodiazepine receptors were of high-affinity, K{sub D} values were 7.5-43 nM and the densities of receptors (B{sub max}) were 924-4131 fmol/mg protein. Astrocytes posses a high-affinity benzodiazepine receptor, K{sub D} values were 6.6-13 nM. The B{sub max} values were 6,033-12,000 fmol/mg protein. The pharmacological profile of the neuronal benzodiazepine receptor was that of the central-type benzodiazepine receptor, where clonazepam has a high-affinity and Ro 5-4864 (4{prime}-chlorodiazepam) has a low-affinity. Whereas astrocytic benzoidazepine receptor was characteristic of the so called peripheral-type benzodiazepine receptors, which shows a high-affinity towards Ro 5-4863, and a low-affinity towards clonazepam. The astrocytic benzodiazepine receptors was functionally correlated with voltage dependent calcium channels, since dihydropyridines and benzodiazepines interacted with ({sup 3}H) diazepam and ({sup 3}H) nitrendipine receptors with the same rank order of potency, showing a statistically significant correlation. No such correlation was observed in neurons.

Identification of Human P2X1 Receptor-interacting Proteins Reveals a Role of the Cytoskeleton in Receptor Regulation*

Science.gov (United States)

Lalo, Ulyana; Roberts, Jonathan A.; Evans, Richard J.

2011-01-01

P2X1 receptors are ATP-gated ion channels expressed by smooth muscle and blood cells. Carboxyl-terminally His-FLAG-tagged human P2X1 receptors were stably expressed in HEK293 cells and co-purified with cytoskeletal proteins including actin. Disruption of the actin cytoskeleton with cytochalasin D inhibited P2X1 receptor currents with no effect on the time course of the response or surface expression of the receptor. Stabilization of the cytoskeleton with jasplakinolide had no effect on P2X1 receptor currents but decreased receptor mobility. P2X2 receptor currents were unaffected by cytochalasin, and P2X1/2 receptor chimeras were used to identify the molecular basis of actin sensitivity. These studies showed that the intracellular amino terminus accounts for the inhibitory effects of cytoskeletal disruption similar to that shown for lipid raft/cholesterol sensitivity. Stabilization of the cytoskeleton with jasplakinolide abolished the inhibitory effects of cholesterol depletion on P2X1 receptor currents, suggesting that lipid rafts may regulate the receptor through stabilization of the cytoskeleton. These studies show that the cytoskeleton plays an important role in P2X1 receptor regulation. PMID:21757694

Serotonin Receptors in Hippocampus

Science.gov (United States)

Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

2012-01-01

Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

Cross-talk between an activator of nuclear receptors-mediated transcription and the D1 dopamine receptor signaling pathway.

Science.gov (United States)

Schmidt, Azriel; Vogel, Robert; Rutledge, Su Jane; Opas, Evan E; Rodan, Gideon A; Friedman, Eitan

2005-03-01

Nuclear receptors are transcription factors that usually interact, in a ligand-dependent manner, with specific DNA sequences located within promoters of target genes. The nuclear receptors can also be controlled in a ligand-independent manner via the action of membrane receptors and cellular signaling pathways. 5-Tetradecyloxy-2-furancarboxylic acid (TOFA) was shown to stimulate transcription from the MMTV promoter via chimeric receptors that consist of the DNA binding domain of GR and the ligand binding regions of the PPARbeta or LXRbeta nuclear receptors (GR/PPARbeta and GR/LXRbeta). TOFA and hydroxycholesterols also modulate transcription from NF-kappaB- and AP-1-controlled reporter genes and induce neurite differentiation in PC12 cells. In CV-1 cells that express D(1) dopamine receptors, D(1) dopamine receptor stimulation was found to inhibit TOFA-stimulated transcription from the MMTV promoter that is under the control of chimeric GR/PPARbeta and GR/LXRbeta receptors. Treatment with the D(1) dopamine receptor antagonist, SCH23390, prevented dopamine-mediated suppression of transcription, and by itself increased transcription controlled by GR/LXRbeta. Furthermore, combined treatment of CV-1 cells with TOFA and SCH23390 increased transcription controlled by the GR/LXRbeta chimeric receptor synergistically. The significance of this in vitro synergy was demonstrated in vivo, by the observation that SCH23390 (but not haloperidol)-mediated catalepsy in rats was potentiated by TOFA, thus showing that an agent that mimics the in vitro activities of compounds that activate members of the LXR and PPAR receptor families can influence D1 dopamine receptor elicited responses.

Lessons from crystal structures of kainate receptors

DEFF Research Database (Denmark)

Møllerud, Stine; Frydenvang, Karla Andrea; Pickering, Darryl S

2017-01-01

Kainate receptors belong to the family of ionotropic glutamate receptors. These receptors assemble from five subunits (GluK1-5) into tetrameric ion channels. Kainate receptors are located at both pre- and postsynaptic membranes in the central nervous system where they contribute to excitatory...... synaptic transmission and modulate network excitability by regulating neurotransmitter release. Dysfunction of kainate receptors has been implicated in several neurological disorders such as epilepsy, schizophrenia and depression. Here we provide a review on the current understanding of kainate receptor...

Nuclear Receptors, RXR, and the Big Bang.

Science.gov (United States)

Evans, Ronald M; Mangelsdorf, David J

2014-03-27

Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the "Big Bang" of molecular endocrinology. This Review provides a personal perspective on nuclear receptors and explores their integrated and coordinated signaling networks that are essential for multicellular life, highlighting the RXR heterodimer and its associated ligands and transcriptional mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Characterization of G-protein coupled receptor kinase interaction with the neurokinin-1 receptor using bioluminescence resonance energy transfer

DEFF Research Database (Denmark)

Jorgensen, Rasmus; Holliday, Nicholas D; Hansen, Jakob L

2007-01-01

To analyze the interaction between the neurokinin-1 (NK-1) receptor and G-protein coupled receptor kinases (GRKs), we performed bioluminescence resonance energy transfer(2) (BRET(2)) measurements between the family A NK-1 receptor and GRK2 and GRK5 as well as their respective kinase-inactive muta......To analyze the interaction between the neurokinin-1 (NK-1) receptor and G-protein coupled receptor kinases (GRKs), we performed bioluminescence resonance energy transfer(2) (BRET(2)) measurements between the family A NK-1 receptor and GRK2 and GRK5 as well as their respective kinase...

Signaling cross-talk between peroxisome proliferator-activated receptor/retinoid X receptor and estrogen receptor through estrogen response elements.

Science.gov (United States)

Keller, H; Givel, F; Perroud, M; Wahli, W

1995-07-01

Peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors (RXRs) are nuclear hormone receptors that are activated by fatty acids and 9-cis-retinoic acid, respectively. PPARs and RXRs form heterodimers that activate transcription by binding to PPAR response elements (PPREs) in the promoter of target genes. The PPREs described thus far consist of a direct tandem repeat of the AGGTCA core element with one intervening nucleotide. We show here that the vitellogenin A2 estrogen response element (ERE) can also function as a PPRE and is bound by a PPAR/RXR heterodimer. Although this heterodimer can bind to several other ERE-related palindromic response elements containing AGGTCA half-sites, only the ERE is able to confer transactivation of test reporter plasmids, when the ERE is placed either close to or at a distance from the transcription initiation site. Examination of natural ERE-containing promoters, including the pS2, very-low-density apolipoprotein II and vitellogenin A2 genes, revealed considerable differences in the binding of PPAR/RXR heterodimers to these EREs. In their natural promoter context, these EREs did not allow transcriptional activation by PPARs/RXRs. Analysis of this lack of stimulation of the vitellogenin A2 promoter demonstrated that PPARs/RXRs bind to the ERE but cannot transactivate due to a nonpermissive promoter structure. As a consequence, PPARs/RXRs inhibit transactivation by the estrogen receptor through competition for ERE binding. This is the first example of signaling cross-talk between PPAR/RXR and estrogen receptor.

Identification and mechanism of ABA receptor antagonism

KAUST Repository

Melcher, Karsten; Xu, Yong; Ng, Ley-Moy; Zhou, X. Edward; Soon, Fen-Fen; Chinnusamy, Viswanathan; Suino-Powell, Kelly M.; Kovach, Amanda; Tham, Fook S.; Cutler, Sean R.; Li, Jun; Yong, Eu-Leong; Zhu, Jian-Kang; Xu, H. Eric

2010-01-01

The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.

Reconstruction of the Chemotaxis Receptor-Kinase Assembly

International Nuclear Information System (INIS)

Park, S.; Borbat, P.; Gonzalez-Bonet, G.; Bhatnagar, J.; Pollard, A.; Freed, J.; Bilwes, A.; Crane, B.

2006-01-01

In bacterial chemotaxis, an assembly of transmembrane receptors, the CheA histidine kinase and the adaptor protein CheW processes environmental stimuli to regulate motility. The structure of a Thermotoga maritima receptor cytoplasmic domain defines CheA interaction regions and metal ion-coordinating charge centers that undergo chemical modification to tune receptor response. Dimeric CheA-CheW, defined by crystallography and pulsed ESR, positions two CheWs to form a cleft that is lined with residues important for receptor interactions and sized to clamp one receptor dimer. CheW residues involved in kinase activation map to interfaces that orient the CheW clamps. CheA regulatory domains associate in crystals through conserved hydrophobic surfaces. Such CheA self-contacts align the CheW receptor clamps for binding receptor tips. Linking layers of ternary complexes with close-packed receptors generates a lattice with reasonable component ratios, cooperative interactions among receptors and accessible sites for modification enzymes

Identification and mechanism of ABA receptor antagonism

KAUST Repository

Melcher, Karsten

2010-08-22

The phytohormone abscisic acid (ABA) functions through a family of fourteen PYR/PYL receptors, which were identified by resistance to pyrabactin, a synthetic inhibitor of seed germination. ABA activates these receptors to inhibit type 2C protein phosphatases, such as ABI1, yet it remains unclear whether these receptors can be antagonized. Here we demonstrate that pyrabactin is an agonist of PYR1 and PYL1 but is unexpectedly an antagonist of PYL2. Crystal structures of the PYL2-pyrabactin and PYL1-pyrabactin-ABI1 complexes reveal the mechanism responsible for receptor-selective activation and inhibition, which enables us to design mutations that convert PYL1 to a pyrabactin-inhibited receptor and PYL2 to a pyrabactin-activated receptor and to identify new pyrabactin-based ABA receptor agonists. Together, our results establish a new concept of ABA receptor antagonism, illustrate its underlying mechanisms and provide a rational framework for discovering novel ABA receptor ligands. © 2010 Nature America, Inc. All rights reserved.

Virally encoded 7TM receptors

DEFF Research Database (Denmark)

Rosenkilde, M M; Waldhoer, M; Lüttichau, H R

2001-01-01

expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets.......A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion...

Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function

International Nuclear Information System (INIS)

Nagayama, Yuji; Wadsworth, H.L.; Chazenbalk, G.D.; Russo, D.; Seto, Pui; Rapoport, B.

1991-01-01

To define the sites in the extracellular domain of the human thyrotropin (TSH) receptor that are involved in TSH binding and signal transduction the authors constructed chimeric thyrotropin-luteinizing hormone/chorionic gonadotropin (TSH-LH/CG) receptors. The extracellular domain of the human TSH receptor was divided into five regions that were replaced, either singly or in various combinations, with homologous regions of the rat LH/CG receptor. The chimeric receptors were stably expressed in Chinese hamster ovary cells. The data obtained suggest that the carboxyl region of the extracellular domain (amino acid residues 261-418) and particularly the middle region (residues 171-260) play a role in signal transduction. The possibility is also raised of an interaction between the amino and carboxyl regions of the extracellular domain in the process of signal transduction. In summary, these studies suggest that the middle region and carboxyl half of the extracellular domain of the TSH receptor are involved in signal transduction and that the TSH-binding region is likely to span the entire extracellular domain, with multiple discontinuous contact sites

Dark chocolate receptors: epicatechin-induced cardiac protection is dependent on delta-opioid receptor stimulation.

Science.gov (United States)

Panneerselvam, Mathivadhani; Tsutsumi, Yasuo M; Bonds, Jacqueline A; Horikawa, Yousuke T; Saldana, Michelle; Dalton, Nancy D; Head, Brian P; Patel, Piyush M; Roth, David M; Patel, Hemal H

2010-11-01

Epicatechin, a flavonoid, is a well-known antioxidant linked to a variety of protective effects in both humans and animals. In particular, its role in protection against cardiovascular disease has been demonstrated by epidemiologic studies. Low-dose epicatechin, which does not have significant antioxidant activity, is also protective; however, the mechanism by which low-dose epicatechin induces this effect is unknown. Our laboratory tested the hypothesis that low-dose epicatechin mediates cardiac protection via opioid receptor activation. C57BL/6 mice were randomly assigned to 1 of 10 groups: control, epicatechin, naloxone (nonselective opioid receptor antagonist), epicatechin + naloxone, naltrindole (δ-specific opioid receptor antagonist), epicatechin + naltrindole, norbinaltorphimine (nor-BNI, κ-specific opioid receptor antagonist), epicatechin + nor-BNI, 5-hydroxydecanoic acid [5-HD, ATP-sensitive potassium channel antagonist], and epicatechin + 5-HD. Epicatechin (1 mg/kg) or other inhibitors (5 mg/kg) were administered by oral gavage or intraperitoneal injection, respectively, daily for 10 days. Mice were subjected to 30 min coronary artery occlusion followed by 2 h of reperfusion, and infarct size was determined via planimetry. Whole heart homogenates were assayed for downstream opioid receptor signaling targets. Infarct size was significantly reduced in epicatechin- and epicatechin + nor-BNI-treated mice compared with control mice. This protection was blocked by naloxone, naltrindole, and 5-HD. Epicatechin and epicatechin + nor-BNI increased the phosphorylation of Src, Akt, and IκBα, while simultaneously decreasing the expression of c-Jun NH(2)-terminal kinase and caspase-activated DNase. All signaling effects are consistent with opioid receptor stimulation and subsequent cardiac protection. Naloxone, naltrindole, and 5-HD attenuated these effects. In conclusion, epicatechin acts via opioid receptors and more specifically through the δ-opioid receptor to

Quantitative densitometry of neurotransmitter receptors

International Nuclear Information System (INIS)

Rainbow, T.C.; Bleisch, W.V.; Biegon, A.; McEwen, B.S.

1982-01-01

An autoradiographic procedure is described that allows the quantitative measurement of neurotransmitter receptors by optical density readings. Frozen brain sections are labeled in vitro with [ 3 H]ligands under conditions that maximize specific binding to neurotransmitter receptors. The labeled sections are then placed against the 3 H-sensitive LKB Ultrofilm to produce the autoradiograms. These autoradiograms resemble those produced by [ 14 C]deoxyglucose autoradiography and are suitable for quantitative analysis with a densitometer. Muscarinic cholinergic receptors in rat and zebra finch brain and 5-HT receptors in rat brain were visualized by this method. When the proper combination of ligand concentration and exposure time are used, the method provides quantitative information about the amount and affinity of neurotransmitter receptors in brain sections. This was established by comparisons of densitometric readings with parallel measurements made by scintillation counting of sections. (Auth.)

Receptor Tyrosine Kinases in Drosophila Development

Science.gov (United States)

Sopko, Richelle; Perrimon, Norbert

2013-01-01

Tyrosine phosphorylation plays a significant role in a wide range of cellular processes. The Drosophila genome encodes more than 20 receptor tyrosine kinases and extensive studies in the past 20 years have illustrated their diverse roles and complex signaling mechanisms. Although some receptor tyrosine kinases have highly specific functions, others strikingly are used in rather ubiquitous manners. Receptor tyrosine kinases regulate a broad expanse of processes, ranging from cell survival and proliferation to differentiation and patterning. Remarkably, different receptor tyrosine kinases share many of the same effectors and their hierarchical organization is retained in disparate biological contexts. In this comprehensive review, we summarize what is known regarding each receptor tyrosine kinase during Drosophila development. Astonishingly, very little is known for approximately half of all Drosophila receptor tyrosine kinases. PMID:23732470

Synergistic Action of Presynaptic Muscarinic Acetylcholine Receptors and Adenosine Receptors in Developmental Axonal Competition at the Neuromuscular Junction.

Science.gov (United States)

Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria Angel; Cilleros, Victor; Tomàs, Josep Maria

2016-01-01

The development of the nervous system involves the initial overproduction of synapses, which promotes connectivity. Hebbian competition between axons with different activities leads to the loss of roughly half of the overproduced elements and this refines connectivity. We used quantitative immunohistochemistry to investigate, in the postnatal day 7 (P7) to P9 neuromuscular junctions, the involvement of muscarinic receptors (muscarinic acetylcholine autoreceptors and the M1, M2, and M4 subtypes) and adenosine receptors (A1 and A2A subtypes) in the control of axonal elimination after the mouse levator auris longus muscle had been exposed to selective antagonists in vivo. In a previous study we analyzed the role of each of the individual receptors. Here we investigate the additive or occlusive effects of their inhibitors and thus the existence of synergistic activity between the receptors. The main results show that the A2A, M1, M4, and A1 receptors (in this order of ability) delayed axonal elimination at P7. M4 produces some occlusion of the M1 pathway and some addition to the A1 pathway, which suggests that they cooperate. M2 receptors may modulate (by allowing a permissive action) the other receptors, mainly M4 and A1. The continued action of these receptors (now including M2 but not M4) finally promotes axonal loss at P9. All 4 receptors (M2, M1, A1, and A2A, in this order of ability) are necessary. The M4 receptor (which in itself does not affect axon loss) seems to modulate the other receptors. We found a synergistic action between the M1, A1, and A2A receptors, which show an additive effect, whereas the potent M2 effect is largely independent of the other receptors (though can be modulated by M4). At P9, there is a full mutual dependence between the A1 and A2A receptors in regulating axon loss. In summary, postnatal axonal elimination is a regulated multireceptor mechanism that involves the cooperation of several muscarinic and adenosine receptor subtypes. �

Benzodiazepine receptor antagonists for hepatic encephalopathy

DEFF Research Database (Denmark)

Als-Nielsen, B; Gluud, L L; Gluud, C

2004-01-01

Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy....

NMDA receptor antagonists inhibit catalepsy induced by either dopamine D1 or D2 receptor antagonists.

Science.gov (United States)

Moore, N A; Blackman, A; Awere, S; Leander, J D

1993-06-11

In the present study, we investigated the ability of NMDA receptor antagonists to inhibit catalepsy induced by haloperidol, or SCH23390 and clebopride, selective dopamine D1 and D2 receptor antagonists respectively. Catalepsy was measured by recording the time the animal remained with its forepaws placed over a rod 6 cm above the bench. Pretreatment with either the non-competitive NMDA receptor antagonist, MK-801 (0.25-0.5 mg/kg i.p.) or the competitive antagonist, LY274614 (10-20 mg/kg i.p.) reduced the cataleptic response produced by haloperidol (10 mg/kg), SCH23390 (2.5-10 mg/kp i.p.) or clebopride (5-20 mg/kg i.p.). This demonstrates that NMDA receptor antagonists will reduce both dopamine D1 and D2 receptor antagonist-induced catalepsy. Muscle relaxant doses of chlordiazepoxide (10 mg/kg i.p.) failed to reduce the catalepsy induced by haloperidol, suggesting that the anticataleptic effect of the NMDA receptor antagonists was not due to a non-specific action. These results support the hypothesis that NMDA receptor antagonists may have beneficial effects in disorders involving reduced dopaminergic function, such as Parkinson's disease.

Life History of the Emerald Jewel Wasp Ampulex compressa

Directory of Open Access Journals (Sweden)

Ryan Arvidson

2018-04-01

Full Text Available The Emerald Jewel Wasp Ampulex compressa (Fabricius is an endoparasitoid of the American cockroach Periplaneta americana (Linnaeus. Its host subjugation strategy is unusual in that envenomation is directed into the host central nervous system, eliciting a long-term behavior modification termed hypokinesia, turning stung cockroaches into a lethargic and compliant, but not paralyzed, living food supply for wasp offspring. A. compressa manipulates hypokinesic cockroaches into a burrow, where it oviposits a single egg onto a mesothoracic leg, hatching three days later. Herein we describe the life history and developmental timing of A. compressa. Using head capsule measurements and observations of mandibular morphology, we found that the larvae develop through three instars, the first two ectoparasitoid, and the third exclusively endoparasitoid. The first two instars have mandibles sufficient for piercing and cutting the cuticle respectively, while the third instar has a larger and blunter mandibular structure. During ecdysis to the third instar, the larva enters the body cavity of the cockroach, consuming internal tissues selectively, including fat body and skeletal muscle, but sparing the gut and Malpighian tubules. The developmental timing to pupation is similar between males and females, but cocoon volume and mass, and pupation duration are sexually dimorphic. Further, we show that the difference in cocoon mass and volume can be used to predict sex before eclosion, which is valuable for studies in venom pharmacology, as only females produce venom.

Identification of Hymenolepis diminuta Cysticercoid Larvae in Tribolium castaneum (Coleoptera: Tenebrionidae) Beetles from Iran.

Science.gov (United States)

Makki, Mahsa Sadat; Mowlavi, Gholamreza; Shahbazi, Farideh; Abai, Mohammad Reza; Najafi, Faezeh; Hosseini-Farash, Bibi Razieh; Teimoori, Salma; Hasanpour, Hamid; Naddaf, Saied Reza

2017-06-01

Hymenolepis diminuta is a cestod of rodents and rarely infects humans. Infection in humans is via ingestion of infected insects. This study was aimed to detect H. diminuta cysticercoids in red flour beetles, Tribolium castaneum, and cockroaches originated from different regions of Iran. The red flour beetles and cockroaches were collected from local bakeries in five cities including Tehran, Ahvaz, Kazerun, and Sabzevar during 2010-2011. Some beetles and cockroaches were colonized in insectary and adults from F1 generation were fed on H. diminuta eggs. Both laboratory-infected and field-collected samples were dissected and examined for cysticercoids. Detection of H. diminuta DNA in T. castaneum beetles was performed by targeting a partial sequence of Ribosomal gene. Except the beetles from Ahvaz, all specimens were negative for cysticercoid by microscopy. Of the four dissected beetles from Ahvaz, one harbored 12 cysticercoids. Also, 110 (52%) of laboratory-infected beetles showed infection with an average of 12-14 larvae. None of the cockroaches was infected. Two beetles from Ahvaz, including the remainder of the microscopic positive specimen, yielded the expected amplicon in PCR assay. The H. diminuta DNA sequences generated in this study were identical and matched 97-100% with similar sequences from GenBank database. Lack of infection in the majority of beetles may reflect a low rat infestation rate in those areas, alternatively, the examined specimens might not have been the representative samples of the T. castaneum populations.

Peroxisome Proliferator-Activated Receptor and Vitamin D Receptor Signaling Pathways in Cancer Cells

Directory of Open Access Journals (Sweden)

Yasuko Kitagishi

2013-10-01

Full Text Available Peroxisome proliferator-activated receptors (PPARs are members of the superfamily of nuclear hormone receptors, which respond to specific ligands such as polyunsaturated fatty acids by altering gene expression. Three subtypes of this receptor have been discovered, each evolving to achieve different biological functions. Like other nuclear receptors, the transcriptional activity of PPARs is affected not only by ligand-stimulation, but also by cross-talk with other molecules. For example, both PPARs and the RXRs are ligand-activated transcription factors that coordinately regulate gene expression. In addition, PPARs and vitamin D receptor (VDR signaling pathways regulate a multitude of genes that are of importance for cellular functions including cell proliferation and cell differentiation. Interaction of the PPARs and VDR signaling pathways has been shown at the level of molecular cross-regulation of their transcription factor. A variety of ligands influencing the PPARs and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in human cancers. Use of these compounds may represent a potential novel strategy to prevent cancers. This review summarizes the roles of the PPARs and the VDR in pathogenesis and progression of cancer.

Peroxisome Proliferator-Activated Receptor and Vitamin D Receptor Signaling Pathways in Cancer Cells

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Satoru, E-mail: smatsuda@cc.nara-wu.ac.jp; Kitagishi, Yasuko [Department of Food Science and Nutrition, Nara Women’s University, Kita-Uoya Nishimachi, Nara 630-8506 (Japan)

2013-10-21

Peroxisome proliferator-activated receptors (PPARs) are members of the superfamily of nuclear hormone receptors, which respond to specific ligands such as polyunsaturated fatty acids by altering gene expression. Three subtypes of this receptor have been discovered, each evolving to achieve different biological functions. Like other nuclear receptors, the transcriptional activity of PPARs is affected not only by ligand-stimulation, but also by cross-talk with other molecules. For example, both PPARs and the RXRs are ligand-activated transcription factors that coordinately regulate gene expression. In addition, PPARs and vitamin D receptor (VDR) signaling pathways regulate a multitude of genes that are of importance for cellular functions including cell proliferation and cell differentiation. Interaction of the PPARs and VDR signaling pathways has been shown at the level of molecular cross-regulation of their transcription factor. A variety of ligands influencing the PPARs and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in human cancers. Use of these compounds may represent a potential novel strategy to prevent cancers. This review summarizes the roles of the PPARs and the VDR in pathogenesis and progression of cancer.

Peroxisome Proliferator-Activated Receptor and Vitamin D Receptor Signaling Pathways in Cancer Cells

International Nuclear Information System (INIS)

Matsuda, Satoru; Kitagishi, Yasuko

2013-01-01

Peroxisome proliferator-activated receptors (PPARs) are members of the superfamily of nuclear hormone receptors, which respond to specific ligands such as polyunsaturated fatty acids by altering gene expression. Three subtypes of this receptor have been discovered, each evolving to achieve different biological functions. Like other nuclear receptors, the transcriptional activity of PPARs is affected not only by ligand-stimulation, but also by cross-talk with other molecules. For example, both PPARs and the RXRs are ligand-activated transcription factors that coordinately regulate gene expression. In addition, PPARs and vitamin D receptor (VDR) signaling pathways regulate a multitude of genes that are of importance for cellular functions including cell proliferation and cell differentiation. Interaction of the PPARs and VDR signaling pathways has been shown at the level of molecular cross-regulation of their transcription factor. A variety of ligands influencing the PPARs and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in human cancers. Use of these compounds may represent a potential novel strategy to prevent cancers. This review summarizes the roles of the PPARs and the VDR in pathogenesis and progression of cancer

Dopamine Receptors and Parkinson's Disease

Directory of Open Access Journals (Sweden)

Shin Hisahara

2011-01-01

Full Text Available Parkinson's disease (PD is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS. In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist.

Nuclear receptor corepressor-dependent repression of peroxisome-proliferator-activated receptor delta-mediated transactivation

DEFF Research Database (Denmark)

Krogsdam, Anne-M; Nielsen, Curt A F; Neve, Søren

2002-01-01

delta-RXR alpha heterodimer bound to an acyl-CoA oxidase (ACO)-type peroxisome-proliferator response element recruited a glutathione S-transferase-NCoR fusion protein in a ligand-independent manner. Contrasting with most other nuclear receptors, PPAR delta was found to interact equally well......The nuclear receptor corepressor (NCoR) was isolated as a peroxisome-proliferator-activated receptor (PPAR) delta interacting protein using the yeast two-hybrid system. NCoR interacted strongly with the ligand-binding domain of PPAR delta, whereas interactions with the ligand-binding domains...

Action mechanisms of Liver X Receptors

Energy Technology Data Exchange (ETDEWEB)

Gabbi, Chiara; Warner, Margaret [Center for Nuclear Receptors and Cell Signaling, University of Houston, 3056 Cullen Blv, 77204 Houston, Texas (United States); Gustafsson, Jan-Åke, E-mail: jgustafs@central.uh.edu [Center for Nuclear Receptors and Cell Signaling, University of Houston, 3056 Cullen Blv, 77204 Houston, Texas (United States); Department of Biosciences and Nutrition, Karolinska Institutet, Novum S-141 86 (Sweden)

2014-04-11

Highlights: • LXRα and LXRβ are ligand-activated nuclear receptors. • They share oxysterol ligands and the same heterodimerization partner, RXR. • LXRs regulate lipid and glucose metabolism, CNS and immune functions, and water transport. - Abstract: The two Liver X Receptors, LXRα and LXRβ, are nuclear receptors belonging to the superfamily of ligand-activated transcription factors. They share more than 78% homology in amino acid sequence, a common profile of oxysterol ligands and the same heterodimerization partner, Retinoid X Receptor. LXRs play crucial roles in several metabolic pathways: lipid metabolism, in particular in preventing cellular cholesterol accumulation; glucose homeostasis; inflammation; central nervous system functions and water transport. As with all nuclear receptors, the transcriptional activity of LXR is the result of an orchestration of numerous cellular factors including ligand bioavailability, presence of corepressors and coactivators and cellular context i.e., what other pathways are activated in the cell at the time the receptor recognizes its ligand. In this mini-review we summarize the factors regulating the transcriptional activity and the mechanisms of action of these two receptors.

Pharmacological analysis of calcium antagonist receptors

International Nuclear Information System (INIS)

Reynolds, I.J.

1987-01-01

This work focuses on two aspects of the action of calcium antagonist drugs, namely, the interaction of drugs with receptors for verapamil-like calcium antagonists, and the interactions of drugs with voltage-sensitive calcium fluxes in rat brain synaptosomes. From binding studies I have found that the ligand of choice for labeling the verapamil receptor is (-)[ 3 H]desmethoxy-verapamil. This drug labels potently, reversibly and stereoselectively two receptors in membranes prepared from rat brain and rabbit skeletal muscle tissues. In equilibrium studies dihydropyridine calcium antagonists interact in a non-competitive fashion, while many non-DHPs are apparently competitive. In-depth kinetic studies in skeletal muscle membranes indicate that the two receptors are linked in a negative heterotropic fashion, and that low-affinity binding of (-) [ 3 H]desmethoxy-verapamil may be to the diltiazem receptor. However, these studies were not able to distinguish between the hypothesis that diltiazem binds to spatially separate, allosterically coupled receptors, and the hypothesis that diltiazem binds to a subsite of the verapamil receptor

Action mechanisms of Liver X Receptors

International Nuclear Information System (INIS)

Gabbi, Chiara; Warner, Margaret; Gustafsson, Jan-Åke

2014-01-01

Highlights: • LXRα and LXRβ are ligand-activated nuclear receptors. • They share oxysterol ligands and the same heterodimerization partner, RXR. • LXRs regulate lipid and glucose metabolism, CNS and immune functions, and water transport. - Abstract: The two Liver X Receptors, LXRα and LXRβ, are nuclear receptors belonging to the superfamily of ligand-activated transcription factors. They share more than 78% homology in amino acid sequence, a common profile of oxysterol ligands and the same heterodimerization partner, Retinoid X Receptor. LXRs play crucial roles in several metabolic pathways: lipid metabolism, in particular in preventing cellular cholesterol accumulation; glucose homeostasis; inflammation; central nervous system functions and water transport. As with all nuclear receptors, the transcriptional activity of LXR is the result of an orchestration of numerous cellular factors including ligand bioavailability, presence of corepressors and coactivators and cellular context i.e., what other pathways are activated in the cell at the time the receptor recognizes its ligand. In this mini-review we summarize the factors regulating the transcriptional activity and the mechanisms of action of these two receptors

Mincle suppresses Toll-like receptor 4 activation.

Science.gov (United States)

Greco, Stephanie H; Mahmood, Syed Kashif; Vahle, Anne-Kristin; Ochi, Atsuo; Batel, Jennifer; Deutsch, Michael; Barilla, Rocky; Seifert, Lena; Pachter, H Leon; Daley, Donnele; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R; Miller, George

2016-07-01

Regulation of Toll-like receptor responses is critical for limiting tissue injury and autoimmunity in both sepsis and sterile inflammation. We found that Mincle, a C-type lectin receptor, regulates proinflammatory Toll-like receptor 4 signaling. Specifically, Mincle ligation diminishes Toll-like receptor 4-mediated inflammation, whereas Mincle deletion or knockdown results in marked hyperresponsiveness to lipopolysaccharide in vitro, as well as overwhelming lipopolysaccharide-mediated inflammation in vivo. Mechanistically, Mincle deletion does not up-regulate Toll-like receptor 4 expression or reduce interleukin 10 production after Toll-like receptor 4 ligation; however, Mincle deletion decreases production of the p38 mitogen-activated protein kinase-dependent inhibitory intermediate suppressor of cytokine signaling 1, A20, and ABIN3 and increases expression of the Toll-like receptor 4 coreceptor CD14. Blockade of CD14 mitigates the increased sensitivity of Mincle(-/-) leukocytes to Toll-like receptor 4 ligation. Collectively, we describe a major role for Mincle in suppressing Toll-like receptor 4 responses and implicate its importance in nonmycobacterial models of inflammation. © Society for Leukocyte Biology.

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors

International Nuclear Information System (INIS)

Jäntti, Maria H.; Mandrika, Ilona; Kukkonen, Jyrki P.

2014-01-01

Highlights: • OX 1 and OX 2 orexin and CB 1 cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX 1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB 1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX 1 , OX 2 and CB 1 receptors, C-terminally fused with either Renilla luciferase or GFP 2 green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB 1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP 2 to CB 1 produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX 1 –OX 2 interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB 1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations

Determination of HIV-1 co-receptor usage.

Science.gov (United States)

Cavarelli, Mariangela; Scarlatti, Gabriella

2014-01-01

Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly the β-chemokine receptor 5 (CCR5) and the α-chemokine receptor 4 (CXCR4). Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. In this chapter, methods to determine the co-receptor usage of HIV-1 variants are described.

Untangling dopamine-adenosine receptor-receptor assembly in experimental parkinsonism in rats

Directory of Open Access Journals (Sweden)

Víctor Fernández-Dueñas

2015-01-01

Full Text Available Parkinson’s disease (PD is a dopaminergic-related pathology in which functioning of the basal ganglia is altered. It has been postulated that a direct receptor-receptor interaction – i.e. of dopamine D2 receptor (D2R with adenosine A2A receptor (A2AR (forming D2R-A2AR oligomers – finely regulates this brain area. Accordingly, elucidating whether the pathology prompts changes to these complexes could provide valuable information for the design of new PD therapies. Here, we first resolved a long-standing question concerning whether D2R-A2AR assembly occurs in native tissue: by means of different complementary experimental approaches (i.e. immunoelectron microscopy, proximity ligation assay and TR-FRET, we unambiguously identified native D2R-A2AR oligomers in rat striatum. Subsequently, we determined that, under pathological conditions (i.e. in a rat PD model, D2R-A2AR interaction was impaired. Collectively, these results provide definitive evidence for alteration of native D2R-A2AR oligomers in experimental parkinsonism, thus conferring the rationale for appropriate oligomer-based PD treatments.

Retinoid X receptor and peroxisome proliferator-activated receptor activate an estrogen responsive gene independent of the estrogen receptor.

Science.gov (United States)

Nuñez, S B; Medin, J A; Braissant, O; Kemp, L; Wahli, W; Ozato, K; Segars, J H

1997-03-14

Estrogen receptors regulate transcription of genes essential for sexual development and reproductive function. Since the retinoid X receptor (RXR) is able to modulate estrogen responsive genes and both 9-cis RA and fatty acids influenced development of estrogen responsive tumors, we hypothesized that estrogen responsive genes might be modulated by RXR and the fatty acid receptor (peroxisome proliferator-activated receptor, PPAR). To test this hypothesis, transfection assays in CV-1 cells were performed with an estrogen response element (ERE) coupled to a luciferase reporter construct. Addition of expression vectors for RXR and PPAR resulted in an 11-fold increase in luciferase activity in the presence of 9-cis RA. Furthermore, mobility shift assays demonstrated binding of RXR and PPAR to the vitellogenin A2-ERE and an ERE in the oxytocin promoter. Methylation interference assays demonstrated that specific guanine residues required for RXR/PPAR binding to the ERE were similar to residues required for ER binding. Moreover, RXR domain-deleted constructs in transfection assays showed that activation required RXR since an RXR delta AF-2 mutant completely abrogated reporter activity. Oligoprecipitation binding studies with biotinylated ERE and (35)S-labeled in vitro translated RXR constructs confirmed binding of delta AF-2 RXR mutant to the ERE in the presence of baculovirus-expressed PPAR. Finally, in situ hybridization confirmed RXR and PPAR mRNA expression in estrogen responsive tissues. Collectively, these data suggest that RXR and PPAR are present in reproductive tissues, are capable of activating estrogen responsive genes and suggest that the mechanism of activation may involve direct binding of the receptors to estrogen response elements.

Atypical chemokine receptors in cancer: friends or foes?

Science.gov (United States)

Massara, Matteo; Bonavita, Ornella; Mantovani, Alberto; Locati, Massimo; Bonecchi, Raffaella

2016-06-01

The chemokine system is a fundamental component of cancer-related inflammation involved in all stages of cancer development. It controls not only leukocyte infiltration in primary tumors but also angiogenesis, cancer cell proliferation, and migration to metastatic sites. Atypical chemokine receptors are a new, emerging class of regulators of the chemokine system. They control chemokine bioavailability by scavenging, transporting, or storing chemokines. They can also regulate the activity of canonical chemokine receptors with which they share the ligands by forming heterodimers or by modulating their expression levels or signaling activity. Here, we summarize recent results about the role of these receptors (atypical chemokine receptor 1/Duffy antigen receptor for chemokine, atypical chemokine receptor 2/D6, atypical chemokine receptor 3/CXC-chemokine receptor 7, and atypical chemokine receptor 4/CC-chemokine receptor-like 1) on the tumorigenesis process, indicating that their effects are strictly dependent on the cell type on which they are expressed and on their coexpression with other chemokine receptors. Indeed, atypical chemokine receptors inhibit tumor growth and progression through their activity as negative regulators of chemokine bioavailability, whereas, on the contrary, they can promote tumorigenesis when they regulate the signaling of other chemokine receptors, such as CXC-chemokine receptor 4. Thus, atypical chemokine receptors are key components of the regulatory network of inflammation and immunity in cancer and may have a major effect on anti-inflammatory and immunotherapeutic strategies. © Society for Leukocyte Biology.

Molecular pharmacology of human NMDA receptors

DEFF Research Database (Denmark)

Hedegaard, Maiken; Hansen, Kasper Bø; Andersen, Karen Toftegaard

2012-01-01

N-methyl-d-aspartate (NMDA) receptors are ionotropic glutamate receptors that mediate excitatory neurotransmission. NMDA receptors are also important drug targets that are implicated in a number of pathophysiological conditions. To facilitate the transition from lead compounds in pre-clinical ani...

The association of metabotropic glutamate receptor type 5 with the neuronal Ca2+-binding protein 2 modulates receptor function.

Science.gov (United States)

Canela, Laia; Fernández-Dueñas, Víctor; Albergaria, Catarina; Watanabe, Masahiko; Lluís, Carme; Mallol, Josefa; Canela, Enric I; Franco, Rafael; Luján, Rafael; Ciruela, Francisco

2009-10-01

Metabotropic glutamate (mGlu) receptors mediate in part the CNS effects of glutamate. These receptors interact with a large array of intracellular proteins in which the final role is to regulate receptor function. Here, using co-immunoprecipitation and pull-down experiments we showed a close and specific interaction between mGlu(5) receptor and NECAB2 in both transfected human embryonic kidney cells and rat hippocampus. Interestingly, in pull-down experiments increasing concentrations of calcium drastically reduced the ability of these two proteins to interact, suggesting that NECAB2 binds to mGlu(5) receptor in a calcium-regulated manner. Immunoelectron microscopy detection of NECAB2 and mGlu(5) receptor in the rat hippocampal formation indicated that both proteins are codistributed in the same subcellular compartment of pyramidal cells. In addition, the NECAB2/mGlu(5) receptor interaction regulated mGlu(5b)-mediated activation of both inositol phosphate accumulation and the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. Overall, these findings indicate that NECAB2 by its physical interaction with mGlu(5b) receptor modulates receptor function.

Coronavirus spike-receptor interactions

NARCIS (Netherlands)

Mou, H.

2015-01-01

Coronaviruses cause important diseases in humans and animals. Coronavirus infection starts with the virus binding with its spike proteins to molecules present on the surface of host cells that act as receptors. This spike-receptor interaction is highly specific and determines the virus’ cell, tissue

Evidence for Heterodimerization and Functional Interaction of the Angiotensin Type 2 Receptor and the Receptor MAS

DEFF Research Database (Denmark)

Leonhardt, Julia; Villela, Daniel C.; Teichmann, Anke

2017-01-01

The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors of the protective arm of the renin-angiotensin system. They mediate strikingly similar actions. Moreover, in various studies, AT2R antagonists blocked the effects of MAS agonists and vice versa. Such cross-inhibition may in...

Steroid Hormone Receptor Signals as Prognosticators for Urothelial Tumor

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Hiroki Ide

2015-01-01

Full Text Available There is a substantial amount of preclinical or clinical evidence suggesting that steroid hormone receptor-mediated signals play a critical role in urothelial tumorigenesis and tumor progression. These receptors include androgen receptor, estrogen receptors, glucocorticoid receptor, progesterone receptor, vitamin D receptor, retinoid receptors, peroxisome proliferator-activated receptors, and others including orphan receptors. In particular, studies using urothelial cancer tissue specimens have demonstrated that elevated or reduced expression of these receptors as well as alterations of their upstream or downstream pathways correlates with patient outcomes. This review summarizes and discusses available data suggesting that steroid hormone receptors and related signals serve as biomarkers for urothelial carcinoma and are able to predict tumor recurrence or progression.

Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M1, M2, and M4 receptor knockout mice.

Science.gov (United States)

Joseph, Lauren; Thomsen, Morgane

2017-06-30

Muscarinic M 1 /M 4 receptor stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (S D ) effects, but the receptor subtypes mediating those effects are not known. A better understanding of the complex cocaine/muscarinic interactions is needed to evaluate and develop potential muscarinic-based medications. Here, knockout mice lacking M 1 , M 2 , or M 4 receptors (M 1 -/- , M 2 -/- , M 4 -/- ), as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline. Muscarinic receptor antagonists with no subtype selectivity (scopolamine), or preferential affinity at the M 1 , M 2 , or M 4 subtype (telenzepine, trihexyphenidyl; methoctramine, AQ-RA 741; tropicamide) were tested alone and in combination with cocaine. In intact animals, antagonists with high affinity at M 1 /M 4 receptors partially substituted for cocaine and increased the S D effect of cocaine, while M 2 -preferring antagonists did not substitute, and reduced the S D effect of cocaine. The cocaine-like effects of scopolamine were absent in M 1 -/- mice. The cocaine S D attenuating effects of methoctramine were absent in M 2 -/- mice and almost absent in M 1 -/- mice. The findings indicate that the cocaine-like S D effects of muscarinic antagonists are primarily mediated through M 1 receptors, with a minor contribution of M 4 receptors. The data also support our previous findings that stimulation of M 1 receptors and M 4 receptors can each attenuate the S D effect of cocaine, and show that this can also be achieved by blocking M 2 autoreceptors, likely via increased acetylcholine release. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein

DEFF Research Database (Denmark)

Jacobsen, Linda; Madsen, P; Moestrup, S K

1996-01-01

the corresponding cDNA. The gene, designated SORL1, maps to chromosome 11q 23/24 and encodes a 2214-residue type 1 receptor containing a furin cleavage site immediately preceding the N terminus determined in the purified protein. The receptor, designated sorLA-1, has a short cytoplasmic tail containing a tyrosine...... density lipoprotein receptor gene family receptors, and 3) six tandemly arranged fibronectin type III repeats also found in certain neural adhesion proteins. sorLA-1 may therefore be classified as a hybrid receptor. Northern blotting revealed specific mRNA transcripts in brain, spinal cord, and testis......The 39-40-kDa receptor-associated protein (RAP) binds to the members of the low density lipoprotein receptor gene family and functions as a specialized endoplasmic reticulum/Golgi chaperone. Using RAP affinity chromatography, we have purified a novel approximately 250-kDa brain protein and isolated...

Data for amino acid alignment of Japanese stingray melanocortin receptors with other gnathostome melanocortin receptor sequences, and the ligand selectivity of Japanese stingray melanocortin receptors

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Akiyoshi Takahashi

2016-06-01

Full Text Available This article contains structure and pharmacological characteristics of melanocortin receptors (MCRs related to research published in “Characterization of melanocortin receptors from stingray Dasyatis akajei, a cartilaginous fish” (Takahashi et al., 2016 [1]. The amino acid sequences of the stingray, D. akajei, MC1R, MC2R, MC3R, MC4R, and MC5R were aligned with the corresponding melanocortin receptor sequences from the elephant shark, Callorhinchus milii, the dogfish, Squalus acanthias, the goldfish, Carassius auratus, and the mouse, Mus musculus. These alignments provide the basis for phylogenetic analysis of these gnathostome melanocortin receptor sequences. In addition, the Japanese stingray melanocortin receptors were separately expressed in Chinese Hamster Ovary cells, and stimulated with stingray ACTH, α-MSH, β-MSH, γ-MSH, δ-MSH, and β-endorphin. The dose response curves reveal the order of ligand selectivity for each stingray MCR.

Large-scale production and study of a synthetic G protein-coupled receptor: Human olfactory receptor 17-4

OpenAIRE

Cook, Brian L.; Steuerwald, Dirk; Kaiser, Liselotte; Graveland-Bikker, Johanna; Vanberghem, Melanie; Berke, Allison P.; Herlihy, Kara; Pick, Horst; Vogel, Horst; Zhang, Shuguang

2009-01-01

Although understanding of the olfactory system has progressed at the level of downstream receptor signaling and the wiring of olfactory neurons, the system remains poorly understood at the molecular level of the receptors and their interaction with and recognition of odorant ligands. The structure and functional mechanisms of these receptors still remain a tantalizing enigma, because numerous previous attempts at the large-scale production of functional olfactory receptors (ORs) have not been...

GABAA receptors, but not dopamine, serotonin or NMDA receptors, are increased in the frontal cortex from schizophrenic subjects

International Nuclear Information System (INIS)

Daen, B.; Hussain, T.; Scarr, E.; Tomaskovic, E.; Kitsoulis, S.; Pavey, G.; Hill, C.; Keks, N.; Opeskin, K.; Copolov, D.L.

1998-01-01

Full text: Having shown changed 5HT 2A receptor density in the frontal cortex (FC) from schizophrenic subjects (1) we now report on further studies of the molecular neuroanatomy of the FC in schizophrenia. We used in situ radioligand binding and autoradiography to measure the density of [ 3 H]8OH-DPAT (1 nM) binding (5HT 1A receptors) and [ 3 H]GR113808 (2.4nM) binding (5HT 4 receptors) in Brodmann's areas (BA) 8, 9 and 10 from 10 schizophrenic and 10 controls subjects. In addition, [ 3 H]muscimol (100 nM) binding (GABA A receptors), [ 3 H]TCP (20nM) binding (NMDA receptors), [ 3 H]SCH 23390 (3nM) binding (DA D 1 like receptors) and [ 3 H]YM-09151-2 (4nM) binding (DA D 2 -like receptors) was measured in BA 9 from 17 schizophrenic and 17 control subjects. Subjects were matched for age and sex and the post-mortem interval for tissue collection did not differ. There was a significant increase (18%) in the density of GABA A receptors in BA 9 from subjects with schizophrenia (p<0.05) with no change in NMDA, dopamine or serotonin receptors. These data support the hypothesis that there are selective changes in neurotransmitter receptors in the FC of subjects with schizophrenia. It is not yet clear if such changes contribute to the pathology of the illness. Copyright (1998) Australian Neuroscience Society

Acetylcholine receptors in the human retina

International Nuclear Information System (INIS)

Hutchins, J.B.; Hollyfield, J.G.

1985-01-01

Evidence for a population of acetylcholine (ACh) receptors in the human retina is presented. The authors have used the irreversible ligand 3 H-propylbenzilylcholine mustard ( 3 H-PrBCM) to label muscarinic receptors. 3 H- or 125 I-alpha-bungarotoxin (alpha-BTx) was used to label putative nicotinic receptors. Muscarinic receptors are apparently present in the inner plexiform layer of the retina. Autoradiographic grain densities are reduced in the presence of saturating concentrations of atropine, quinuclidinyl benzilate or scopolamine; this indicates that 3 H-PrBCM binding is specific for a population of muscarinic receptors in the human retina. Binding sites for radiolabeled alpha-BTx are found predominantly in the inner plexiform layer of the retina. Grain densities are reduced in the presence of d-tubocurarine, indicating that alpha-BTx may bind to a pharmacologically relevant nicotinic ACh receptor. This study provides evidence for cholinergic neurotransmission in the human retina

Xenobiotics and the Glucocorticoid Receptor

International Nuclear Information System (INIS)

Gulliver, Linda S M

2017-01-01

Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

Xenobiotics and the Glucocorticoid Receptor

Energy Technology Data Exchange (ETDEWEB)

Gulliver, Linda S M, E-mail: linda.gulliver@otago.ac.nz

2017-03-15

Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

Quantum chemical study of agonist-receptor vibrational interactions for activation of the glutamate receptor.

Science.gov (United States)

Kubo, M; Odai, K; Sugimoto, T; Ito, E

2001-06-01

To understand the mechanism of activation of a receptor by its agonist, the excitation and relaxation processes of the vibrational states of the receptor should be examined. As a first approach to this problem, we calculated the normal vibrational modes of agonists (glutamate and kainate) and an antagonist (6-cyano-7-nitroquinoxaline-2,3-dione: CNQX) of the glutamate receptor, and then investigated the vibrational interactions between kainate and the binding site of glutamate receptor subunit GluR2 by use of a semiempirical molecular orbital method (MOPAC2000-PM3). We found that two local vibrational modes of kainate, which were also observed in glutamate but not in CNQX, interacted through hydrogen bonds with the vibrational modes of GluR2: (i) the bending vibration of the amine group of kainate, interacting with the stretching vibration of the carboxyl group of Glu705 of GluR2, and (ii) the symmetric stretching vibration of the carboxyl group of kainate, interacting with the bending vibration of the guanidinium group of Arg485. We also found collective modes with low frequency at the binding site of GluR2 in the kainate-bound state. The vibrational energy supplied by an agonist may flow from the high-frequency local modes to the low-frequency collective modes in a receptor, resulting in receptor activation.

Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists.

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Gunnar Kleinau

Full Text Available Trace amine-associated receptors (TAAR are rhodopsin-like G-protein-coupled receptors (GPCR. TAAR are involved in modulation of neuronal, cardiac and vascular functions and they are potentially linked with neurological disorders like schizophrenia and Parkinson's disease. Subtype TAAR1, the best characterized TAAR so far, is promiscuous for a wide set of ligands and is activated by trace amines tyramine (TYR, phenylethylamine (PEA, octopamine (OA, but also by thyronamines, dopamine, and psycho-active drugs. Unfortunately, effects of trace amines on signaling of the two homologous β-adrenergic receptors 1 (ADRB1 and 2 (ADRB2 have not been clarified yet in detail. We, therefore, tested TAAR1 agonists TYR, PEA and OA regarding their effects on ADRB1/2 signaling by co-stimulation studies. Surprisingly, trace amines TYR and PEA are partial allosteric antagonists at ADRB1/2, whereas OA is a partial orthosteric ADRB2-antagonist and ADRB1-agonist. To specify molecular reasons for TAAR1 ligand promiscuity and for observed differences in signaling effects on particular aminergic receptors we compared TAAR, tyramine (TAR octopamine (OAR, ADRB1/2 and dopamine receptors at the structural level. We found especially for TAAR1 that the remarkable ligand promiscuity is likely based on high amino acid similarity in the ligand-binding region compared with further aminergic receptors. On the other hand few TAAR specific properties in the ligand-binding site might determine differences in ligand-induced effects compared to ADRB1/2. Taken together, this study points to molecular details of TAAR1-ligand promiscuity and identified specific trace amines as allosteric or orthosteric ligands of particular β-adrenergic receptor subtypes.

Angiotensin type 2 receptors

DEFF Research Database (Denmark)

Sumners, Colin; de Kloet, Annette D; Krause, Eric G

2015-01-01

In most situations, the angiotensin AT2-receptor (AT2R) mediates physiological actions opposing those mediated by the AT1-receptor (AT1R), including a vasorelaxant effect. Nevertheless, experimental evidence vastly supports that systemic application of AT2R-agonists is blood pressure neutral...

Microbiota epitope similarity either dampens or enhances the immunogenicity of disease-associated antigenic epitopes.

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Sebastian Carrasco Pro

Full Text Available The microbiome influences adaptive immunity and molecular mimicry influences T cell reactivity. Here, we evaluated whether the sequence similarity of various antigens to the microbiota dampens or increases immunogenicity of T cell epitopes. Sets of epitopes and control sequences derived from 38 antigenic categories (infectious pathogens, allergens, autoantigens were retrieved from the Immune Epitope Database (IEDB. Their similarity to microbiome sequences was calculated using the BLOSUM62 matrix. We found that sequence similarity was associated with either dampened (tolerogenic; e.g. most allergens or increased (inflammatory; e.g. Dengue and West Nile viruses likelihood of a peptide being immunogenic as a function of epitope source category. Ten-fold cross-validation and validation using sets of manually curated epitopes and non-epitopes derived from allergens were used to confirm these initial observations. Furthermore, the genus from which the microbiome homologous sequences were derived influenced whether a tolerogenic versus inflammatory modulatory effect was observed, with Fusobacterium most associated with inflammatory influences and Bacteroides most associated with tolerogenic influences. We validated these effects using PBMCs stimulated with various sets of microbiome peptides. "Tolerogenic" microbiome peptides elicited IL-10 production, "inflammatory" peptides elicited mixed IL-10/IFNγ production, while microbiome epitopes homologous to self were completely unreactive for both cytokines. We also tested the sequence similarity of cockroach epitopes to specific microbiome sequences derived from households of cockroach allergic individuals and non-allergic controls. Microbiomes from cockroach allergic households were less likely to contain sequences homologous to previously defined cockroach allergens. These results are compatible with the hypothesis that microbiome sequences may contribute to the tolerization of T cells for allergen

Imaging of receptors in clinical neurosciences

NARCIS (Netherlands)

Korf, J

This article deals with the question why should one determine receptors in the brain with positron and single photon emission tomography (PET and SPECT, respectively). Radiopharmaceuticals for a wide variety of receptors are available now. Receptors studies with PET and SPECT have thus far focused

Characterization of glucagon-like peptide-1 receptor beta-arrestin 2 interaction: a high-affinity receptor phenotype

DEFF Research Database (Denmark)

Jorgensen, Rasmus; Martini, Lene; Schwartz, Thue W

2005-01-01

To dissect the interaction between beta-arrestin ((beta)arr) and family B G protein-coupled receptors, we constructed fusion proteins between the glucagon-like peptide 1 receptor and (beta)arr2. The fusion constructs had an increase in apparent affinity selectively for glucagon, suggesting...... that (beta)arr2 interaction locks the receptor in a high-affinity conformation, which can be explored by some, but not all, ligands. The fusion constructs adopted a signaling phenotype governed by the tethered (beta)arr2 with an attenuated G protein-mediated cAMP signal and a higher maximal internalization...... of that which has previously been characterized for family A G protein-coupled receptors, suggesting similarities in the effect of (beta)arr interaction between family A and B receptors also at the molecular level....

Modelling the interdependence between the stoichiometry of receptor oligomerization and ligand binding for a coexisting dimer/tetramer receptor system.

Science.gov (United States)

Rovira, X; Vivó, M; Serra, J; Roche, D; Strange, P G; Giraldo, J

2009-01-01

Many G protein-coupled receptors have been shown to exist as oligomers, but the oligomerization state and the effects of this on receptor function are unclear. For some G protein-coupled receptors, in ligand binding assays, different radioligands provide different maximal binding capacities. Here we have developed mathematical models for co-expressed dimeric and tetrameric species of receptors. We have considered models where the dimers and tetramers are in equilibrium and where they do not interconvert and we have also considered the potential influence of the ligands on the degree of oligomerization. By analogy with agonist efficacy, we have considered ligands that promote, inhibit or have no effect on oligomerization. Cell surface receptor expression and the intrinsic capacity of receptors to oligomerize are quantitative parameters of the equations. The models can account for differences in the maximal binding capacities of radioligands in different preparations of receptors and provide a conceptual framework for simulation and data fitting in complex oligomeric receptor situations.

Evidence for Heterodimerization and Functional Interaction of the Angiotensin Type 2 Receptor and the Receptor MAS.

Science.gov (United States)

Leonhardt, Julia; Villela, Daniel C; Teichmann, Anke; Münter, Lisa-Marie; Mayer, Magnus C; Mardahl, Maibritt; Kirsch, Sebastian; Namsolleck, Pawel; Lucht, Kristin; Benz, Verena; Alenina, Natalia; Daniell, Nicholas; Horiuchi, Masatsugu; Iwai, Masaru; Multhaup, Gerhard; Schülein, Ralf; Bader, Michael; Santos, Robson A; Unger, Thomas; Steckelings, Ulrike Muscha

2017-06-01

The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors of the protective arm of the renin-angiotensin system. They mediate strikingly similar actions. Moreover, in various studies, AT2R antagonists blocked the effects of MAS agonists and vice versa. Such cross-inhibition may indicate heterodimerization of these receptors. Therefore, this study investigated the molecular and functional interplay between MAS and the AT2R. Molecular interactions were assessed by fluorescence resonance energy transfer and by cross correlation spectroscopy in human embryonic kidney-293 cells transfected with vectors encoding fluorophore-tagged MAS or AT2R. Functional interaction of AT2R and MAS was studied in astrocytes with CX3C chemokine receptor-1 messenger RNA expression as readout. Coexpression of fluorophore-tagged AT2R and MAS resulted in a fluorescence resonance energy transfer efficiency of 10.8 ± 0.8%, indicating that AT2R and MAS are capable to form heterodimers. Heterodimerization was verified by competition experiments using untagged AT2R and MAS. Specificity of dimerization of AT2R and MAS was supported by lack of dimerization with the transient receptor potential cation channel, subfamily C-member 6. Dimerization of the AT2R was abolished when it was mutated at cysteine residue 35. AT2R and MAS stimulation with the respective agonists, Compound 21 or angiotensin-(1-7), significantly induced CX3C chemokine receptor-1 messenger RNA expression. Effects of each agonist were blocked by an AT2R antagonist (PD123319) and also by a MAS antagonist (A-779). Knockout of a single of these receptors made astrocytes unresponsive for both agonists. Our results suggest that MAS and the AT2R form heterodimers and that-at least in astrocytes-both receptors functionally depend on each other. © 2017 American Heart Association, Inc.

The cellular receptors of exogenous RNA

Directory of Open Access Journals (Sweden)

Patryk Reniewicz

2016-04-01

Full Text Available One of the key determinants of survival for organisms is proper recognition of exogenous and endogenous nucleic acids. Therefore, high eukaryotes developed a number of receptors that allow for discrimination between friend or foe DNA and RNA. Appearance of exogenous RNA in cytoplasm provides a signal of danger and triggers cellular responses that facilitate eradication of a pathogen. Recognition of exogenous RNA is additionally complicated by fact that large amount of endogenous RNA is present in cytoplasm Thus, number of different receptors, found in eukaryotic cells, is able to recognize that nucleic acid. First group of those receptors consist endosomal Toll like receptors, namely TLR3, TLR7, TLR8 and TLR13. Those receptors recognize RNA released from pathogens that enter the cell by endocytosis. The second group includes cytoplasmic sensors like PKR and the family of RLRs comprised of RIG-I, MDA5 and LGP2. Cytoplasmic receptors recognize RNA from pathogens invading the cell by non-endocytic pathway. In both cases binding of RNA by its receptors results in activation of the signalling cascades that lead to the production of interferon and other cytokines.

G-protein-coupled receptors for free fatty acids

DEFF Research Database (Denmark)

Milligan, Graeme; Ulven, Trond; Murdoch, Hannah

2014-01-01

of these receptors. However, ongoing clinical trials of agonists of free fatty acid receptor 1 suggest that this receptor and other receptors for free fatty acids may provide a successful strategy for controlling hyperglycaemia and providing novel approaches to treat diabetes. Receptors responsive to free fatty acid...

Primary structure and functional characterization of a Drosophila dopamine receptor with high homology to human D1/5 receptors.

Science.gov (United States)

Gotzes, F; Balfanz, S; Baumann, A

1994-01-01

Members of the superfamily of G-protein coupled receptors share significant similarities in sequence and transmembrane architecture. We have isolated a Drosophila homologue of the mammalian dopamine receptor family using a low stringency hybridization approach. The deduced amino acid sequence is approximately 70% homologous to the human D1/D5 receptors. When expressed in HEK 293 cells, the Drosophila receptor stimulates cAMP production in response to dopamine application. This effect was mimicked by SKF 38393, a specific D1 receptor agonist, but inhibited by dopaminergic antagonists such as butaclamol and flupentixol. In situ hybridization revealed that the Drosophila dopamine receptor is highly expressed in the somata of the optic lobes. This suggests that the receptor might be involved in the processing of visual information and/or visual learning in invertebrates.

Demonstration of functional low-density lipoprotein receptors by protein blotting in fibroblasts from a subject with homozygous receptor-negative familial hypercholesterolemia

International Nuclear Information System (INIS)

Semenkovich, C.F.; Ostlund, R.E. Jr.; Yang, J.; Reaban, M.E.

1985-01-01

We report the detection of low-density lipoprotein (LDL) receptors by the technique of receptor blotting in fibroblasts from a patient with homozygous familial hypercholesterolemia (FHC) previously classified as ''receptor negative.'' Solubilized receptors were electrophoresed, transferred to nitrocellulose paper, treated with LDL followed by radiolabeled antibody to LDL, and visualized by autoradiography. GM 2000 FHC fibroblasts revealed LDL receptors with an apparent molecular weight of approximately 140,000, the same as in normal cells. LDL receptor activity by blotting in GM 2000 cells was greatly diminished in comparison with normal cells, but was calcium dependent. Receptor activity was also detectable by conventional monolayer binding and degradation assays. Thus, GM 2000 cells have profoundly diminished LDL receptor activity, but retain the genetic capacity to make LDL receptor material of normal molecular weight that is capable of binding LDL. Previous studies have demonstrated the presence of trace amounts of immunoreactive LDL receptor protein in fibroblasts from some receptor-negative FHC homozygotes. These studies are extended by demonstrating the ability of this material to bind LDL

Microglia P2Y13 Receptors Prevent Astrocyte Proliferation Mediated by P2Y1 Receptors

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Clara Quintas

2018-05-01

Full Text Available Cerebral inflammation is a common feature of several neurodegenerative diseases that requires a fine interplay between astrocytes and microglia to acquire appropriate phenotypes for an efficient response to neuronal damage. During brain inflammation, ATP is massively released into the extracellular medium and converted into ADP. Both nucleotides acting on P2 receptors, modulate astrogliosis through mechanisms involving microglia-astrocytes communication. In previous studies, primary cultures of astrocytes and co-cultures of astrocytes and microglia were used to investigate the influence of microglia on astroglial proliferation induced by ADPβS, a stable ADP analog. In astrocyte cultures, ADPβS increased cell proliferation through activation of P2Y1 and P2Y12 receptors, an effect abolished in co-cultures (of astrocytes with ∼12.5% microglia. The possibility that the loss of the ADPβS-mediated effect could have been caused by a microglia-induced degradation of ADPβS or by a preferential microglial localization of P2Y1 or P2Y12 receptors was excluded. Since ADPβS also activates P2Y13 receptors, the contribution of microglial P2Y13 receptors to prevent the proliferative effect of ADPβS in co-cultures was investigated. The results obtained indicate that P2Y13 receptors are low expressed in astrocytes and mainly expressed in microglia. Furthermore, in co-cultures, ADPβS induced astroglial proliferation in the presence of the selective P2Y13 antagonist MRS 2211 (3 μM and of the selective P2Y12 antagonist AR-C66096 (0.1 μM, suggesting that activation of microglial P2Y12 and P2Y13 receptors may induce the release of messengers that inhibit astroglial proliferation mediated by P2Y1,12 receptors. In this microglia-astrocyte paracrine communication, P2Y12 receptors exert opposite effects in astroglial proliferation as a result of its cellular localization: cooperating in astrocytes with P2Y1 receptors to directly stimulate proliferation and in

Receptor-like kinase SOBIR1/EVR interacts with receptor-like proteins in plant immunity against fungal infection

NARCIS (Netherlands)

Liebrand, T.W.H.; Berg, van den G.C.M.; Zhang, Z.; Smit, P.; Cordewener, J.H.G.; America, A.H.P.; Sklenar, J.; Jones, A.M.E.; Tameling, W.I.L.; Robatzek, S.; Thomma, B.P.H.J.; Joosten, M.H.A.J.

2013-01-01

The plant immune system is activated by microbial patterns that are detected as nonself molecules. Such patterns are recognized by immune receptors that are cytoplasmic or localized at the plasma membrane. Cell surface receptors are represented by receptor-like kinases (RLKs) that frequently contain

Nuclear receptors and nonalcoholic fatty liver disease1

Science.gov (United States)

Cave, Matthew C.; Clair, Heather B.; Hardesty, Josiah E.; Falkner, K. Cameron; Feng, Wenke; Clark, Barbara J.; Sidey, Jennifer; Shi, Hongxue; Aqel, Bashar A.; McClain, Craig J.; Prough, Russell A.

2016-01-01

Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic

Human dopamine receptor and its uses

Energy Technology Data Exchange (ETDEWEB)

Civelli, Olivier (Portland, OR); Van Tol, Hubert Henri-Marie (Toronto, CA)

1999-01-01

The present invention is directed toward the isolation, characterization and pharmacological use of the human D4 dopamine receptor. The nucleotide sequence of the gene corresponding to this receptor and alleleic variant thereof are provided by the invention. The invention also includes recombinant eukaryotic expression constructs capable of expressing the human D4 dopamine receptor in cultures of transformed eukaryotic cells. The invention provides cultures of transformed eukaryotic cells which synthesize the human D4 dopamine receptor, and methods for characterizing novel psychotropic compounds using such cultures.

Receptor study of psychiatric disorders using PET

International Nuclear Information System (INIS)

Suhara, Tetsuya

1992-01-01

Recent receptor studies of psychiatric disorders using PET have been focused on the change in the number of D 2 dopamine receptors in the striatum of drug-naive schizophrenic patients. One study confirmed an increase in D 2 receptors, while another study denied it. Although there were some differences in the approaches of the two groups, the reason for the discrepancy is not clear yet. Looking to psychiatric disorders other than schizophrenia, our recent study revealed a possible role of dopamine D 1 receptors in bipolar mood disorders. However, some problems must be resolved for further receptor studies with PET. For example, our recent study shows that desipamine decreases the in vivo binding of dopramine D 1 and D 2 receptors whereas these is no effect on dopamine D 1 and D 2 receptors in vitro. Additionally significant methodological problems lie in the method of evaluation of the non-specific binding and the effect of endogenous neurotransmitters. Moreover, difficulties in the diagnosis of psychiatric disorders and ethical problems in psychiatric research are critical factors in receptor studies with PET in psychiatric disorders. (author)

Interaction of GABAA receptors with purinergic P2X2 receptors

International Nuclear Information System (INIS)

Shrivastava, A.

2010-01-01

GABA A Rs in the spinal cord are evolving as an important target for drug development against pain. Purinergic P2X 2 Rs are also expressed in spinal cord neurons and are known to cross-talk with GABA A Rs. Here we investigated a possible 'dynamic' interaction between GABA A Rs and P2X 2 Rs using co-immunoprecipitation and FRET studies in HEK cells along with co-localization and single particle tracking studies in spinal cord neurons. Our results suggest that a significant proportion of P2X 2 Rs forms a transient complex with GABA A Rs inside the cell, thus stabilizing these receptors and using them for co-trafficking to the cell surface. P2X 2 Rs and GABA A Rs are then co-inserted into the cell membrane and are primarily located extra-synaptically. Furthermore, agonist induced activation of P2X 2 Rs results in disassembly of the receptor complex and destabilization of GABA A Rs whereas P2X 2 Rs are stabilized and form larger clusters. Antagonist-induced blocking of P2XRs results in co-stabilization of this receptor complex at the cell surface. These results suggest a novel mechanism where association of P2XRs with other receptors could be used for specific targeting to the neuronal membrane, thus providing an extrasynaptic receptor reserve that could regulate the excitability of neurons. We further conclude that blocking the excitatory activity of excessively released ATP under diseased state by P2XR antagonists could simultaneously enhance synaptic inhibition mediated by GABA A Rs.(author) (author) [de

Multiple autophosphorylation sites of the epidermal growth factor receptor are essential for receptor kinase activity and internalization. Contrasting significance of tyrosine 992 in the native and truncated receptors

DEFF Research Database (Denmark)

Sorkin, A; Helin, K; Waters, C M

1992-01-01

The role of epidermal growth factor (EGF) receptor autophosphorylation sites in the regulation of receptor functions has been studied using cells transfected with mutant EGF receptors. Simultaneous point mutation of 4 tyrosines (Y1068, Y1086, Y1148, Y1173) to phenylalanine, as well as removal of ...

Localization of mineralocorticoid receptors at mammalian synapses.

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Eric M Prager

Full Text Available In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids.

Utilisation des blattes et des termites comme substituts potentiels de la farine de viande dans l'alimentation des poulets de chair au Sud-Kivu, République démocratique du Congo

Directory of Open Access Journals (Sweden)

Munyuli Bin Mushambanyi, T.

2002-01-01

Full Text Available Use of Cockroach and Termites as Potential Substitutes of Meal Meat in Broilers Feeding, in South-Kivu, Democratic Republic of the Congo. The objective of this study is to compare some economic and zootechnical parameters obtained by broilers fed with locally prepared rations, with commercial ration or with a local ration with 20% meal meat. The meal meat is very expensive on the local market. The locally prepared and used rations contain 4.8 and 12% of incorpored cockroach meal or 4.8 and 12% of termites meal. The use of 8 and 12% containing cockroach meal rations and those containing 12% of termites meal give satisfactory result in terms of return on investment (ranging between 60 and 100% and mean gain weight, both significant with respect to commercial rations from Tanzania and local rations containing 20% of incorpored meal meat. These rations are profitable, cheaper than commercial rations; they can be adopted by chickens breeders in order to improve profitability in the farming of birds in South-Kivu.

Some theoretical aspects of hormone receptor determination

International Nuclear Information System (INIS)

Sluiter, W.J.

1981-01-01

Suitable antisera for determination of hormone receptors are not available for the majority of hormone receptors. Therefore, the determination of hormone receptors is mostly performed in terms of binding capacity for the appropriate hormone, using radioactive hormone labels. Some theoretical aspects of such a receptor determination are discussed including the length of incubation (total or unoccupied receptor concentration), single point or multiple point (Scatchard) analysis (regarding the influence of other specific binders), the correction procedure for non-specific binding and the influence of the circulating hormone level. (Auth.)

Muscarinic Receptor Signaling in Colon Cancer

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Rosenvinge, Erik C. von, E-mail: evonrose@medicine.umaryland.edu; Raufman, Jean-Pierre [University of Maryland School of Medicine, Division of Gastroenterology & Hepatology, 22 S. Greene Street, N3W62, Baltimore, MD 21201 (United States); Department of Veterans Affairs, VA Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201 (United States)

2011-03-02

According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

Muscarinic Receptor Signaling in Colon Cancer

International Nuclear Information System (INIS)

Rosenvinge, Erik C. von; Raufman, Jean-Pierre

2011-01-01

According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer

Muscarinic Receptor Signaling in Colon Cancer

Directory of Open Access Journals (Sweden)

Jean-Pierre Raufman

2011-03-01

Full Text Available According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

Channel opening of γ-aminobutyric acid receptor from rat brain: molecular mechanisms of the receptor responses

International Nuclear Information System (INIS)

Cash, D.J.; Subbarao, K.

1987-01-01

The function of γ-aminobutyric acid (GABA) receptors, which mediate transmembrane chloride flux, can be studied by use of 36 Cl - isotope tracer with membrane from mammalian brain by quench-flow technique, with reaction times that allow resolution of the receptor desensitization rates from the ion flux rates. The rates of chloride exchange into the vesicles in the absence and presence of GABA were characterized with membrane from rat cerebral cortex. Unspecific 36 Cl - influx was completed in three phases of ca. 3% (t/sub 1/2/ = 0.6 s), 56% (t/sub 1/2 = 82 s), and 41% (t/sub 1/2 = 23 min). GABA-mediated, specific chloride exchange occurred with 6.5% of the total vesicular internal volume. The GABA-dependent 36 Cl - influx proceeded in two phases, each progressively slowed by desensitization. The measurements supported the presence of two distinguishable active GABA receptors on the same membrane mediating chloride exchange into the vesicles. The half-response concentrations were similar for both receptors. The two receptors were present in the activity ratio of ca. 4/1, similar to the ratio of low affinity to high-affinity GABA sites found in ligand binding experiments. The desensitization rates have a different dependence on GABA concentration than the channel-opening equilibria. For both receptors, the measurements over a 2000-fold GABA concentration range required a minimal mechanism involving the occupation of both of the two GABA binding sites for significant channel opening; then the receptors were ca. 80% open. Similarly for both receptors, desensitization was mediated by a different pair of binding sites, although desensitization with only one ligand molecule bound could occur at a 20-fold slower rate

Genotype-Dependent Difference in 5-HT2C Receptor-Induced Hypolocomotion: Comparison with 5-HT2A Receptor Functional Activity

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Darya V. Bazovkina

2015-01-01

Full Text Available In the present study behavioral effects of the 5-HT2C serotonin receptor were investigated in different mouse strains. The 5-HT2C receptor agonist MK-212 applied intraperitoneally induced significant dose-dependent reduction of distance traveled in the open field test in CBA/Lac mice. This effect was receptor-specific because it was inhibited by the 5-HT2C receptor antagonist RS102221. To study the role of genotype in 5-HT2C receptor-induced hypolocomotion, locomotor activity of seven inbred mouse strains was measured after MK-212 acute treatment. We found that the 5-HT2C receptor stimulation by MK-212 decreased distance traveled in the open field test in CBA/Lac, C57Bl/6, C3H/He, and ICR mice, whereas it failed to affect locomotor activity in DBA/2J, Asn, and Balb/c mice. We also compared the interstrain differences in functional response to 5-HT2C and 5-HT2A receptors activation measured by the quantification of receptor-mediated head-twitches. These experiments revealed significant positive correlation between 5-HT2C and 5-HT2A receptors functional responses for all investigated mouse strains. Moreover, we found that 5-HT2A receptor activation with DOI did not change locomotor activity in CBA/Lac mice. Taken together, our data indicate the implication of 5-HT2C receptors in regulation of locomotor activity and suggest the shared mechanism for functional responses mediated by 5-HT2C and 5-HT2A receptors.

Molecular analysis of the nerve growth factor receptor

International Nuclear Information System (INIS)

Hempstead, B.; Patil, N.; Olson, K.; Chao, M.

1988-01-01

An essential molecule in the translocation of information by nerve growth factor (NGF) to responsive cells is the cell-surface receptor for NGF. This paper presents information on the genomic structure of the NGF receptor gene, NGF receptor models, and transfection of NGF receptors. Equilibrium binding of [ 125 I]NGF to cells reveals two distinct affinity states for the NGF receptor. The human NGF receptor gene is a single-copy gene, consisting of six exons that span 23 kb. The receptor gene is capable of being transferred to fibroblast cells from human genomic DNA and expressed at high levels. The constitutive nature of the receptor promoter sequence is a partial explanation of why this tissue-specific gene is expressed efficiently in a variety of nonneuronal cells after genomic gene transfer. The two kinetic forms of the NGF receptor appear to be encoded by the same protein, which is the product of a single gene

Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart.

OpenAIRE

Ping, P; Gelzer-Bell, R; Roth, D A; Kiel, D; Insel, P A; Hammond, H K

1995-01-01

To determine whether beta-adrenergic receptor agonist activation influences guanosine 5'-triphosphate-binding protein (G-protein) expression and beta-adrenergic receptor kinase activity in the heart, we examined the effects of chronic beta 1-adrenergic receptor antagonist treatment (bisoprolol, 0.2 mg/kg per d i.v., 35 d) on components of the myocardial beta-adrenergic receptor-G-protein-adenylyl cyclase pathway in porcine myocardium. Three novel alterations in cardiac adrenergic signaling as...

The G protein-coupled receptors deorphanization landscape.

Science.gov (United States)

Laschet, Céline; Dupuis, Nadine; Hanson, Julien

2018-07-01

G protein-coupled receptors (GPCRs) are usually highlighted as being both the largest family of membrane proteins and the most productive source of drug targets. However, most of the GPCRs are understudied and hence cannot be used immediately for innovative therapeutic strategies. Besides, there are still around 100 orphan receptors, with no described endogenous ligand and no clearly defined function. The race to discover new ligands for these elusive receptors seems to be less intense than before. Here, we present an update of the various strategies employed to assign a function to these receptors and to discover new ligands. We focus on the recent advances in the identification of endogenous ligands with a detailed description of newly deorphanized receptors. Replication being a key parameter in these endeavors, we also discuss the latest controversies about problematic ligand-receptor pairings. In this context, we propose several recommendations in order to strengthen the reporting of new ligand-receptor pairs. Copyright © 2018 Elsevier Inc. All rights reserved.

Nanodiscs for immobilization of lipid bilayers and membrane receptors: kinetic analysis of cholera toxin binding to a glycolipid receptor

DEFF Research Database (Denmark)

Borch, Jonas; Torta, Federico; Sligar, Stephen G

2008-01-01

nanodiscs and their incorporated membrane receptors can be attached to surface plasmon resonance sensorchips and used to measure the kinetics of the interaction between soluble molecules and membrane receptors inserted in the bilayer of nanodiscs. Cholera toxin and its glycolipid receptor G(M1) constitute...... a system that can be considered a paradigm for interactions of soluble proteins with membrane receptors. In this work, we have investigated different technologies for capturing nanodiscs containing the glycolipid receptor G(M1) in lipid bilayers, enabling measurements of binding of its soluble interaction...

Activation-induced proteolysis of cytoplasmic domain of zeta in T cell receptors and Fc receptors.

Science.gov (United States)

Taupin, J L; Anderson, P

1994-12-01

The CD3-T cell receptor (TCR) complex on T cells and the Fc gamma receptor type III (Fc gamma RIII)-zeta-gamma complex on natural killer cells are functionally analogous activation receptors that associate with a family of disulfide-linked dimers composed of the related subunits zeta and gamma. Immunochemical analysis of receptor complexes separated on two-dimensional diagonal gels allowed the identification of a previously uncharacterized zeta-p14 heterodimer. zeta-p14 is a component of both CD3-TCR and Fc gamma RIII-zeta-gamma. Peptide mapping analysis shows that p14 is structurally related to zeta, suggesting that it is either: (i) derived from zeta proteolytically or (ii) the product of an alternatively spliced mRNA. The observation that COS cells transformed with a cDNA encoding zeta express zeta-p14 supports the former possibility. The expression of CD3-TCR complexes including zeta-p14 increases following activation with phorbol 12-myristate 13-acetate or concanavalin A, suggesting that proteolysis of zeta may contribute to receptor modulation or desensitization.

Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways.

Science.gov (United States)

Tomàs, Josep; Garcia, Neus; Lanuza, Maria A; Santafé, Manel M; Tomàs, Marta; Nadal, Laura; Hurtado, Erica; Simó-Ollé, Anna; Cilleros-Mañé, Víctor; Just-Borràs, Laia

2018-01-01

In the last few years, we have studied the presence and involvement in synaptogenesis and mature transmitter release of the adenosine autoreceptors (AR) in the mammalian neuromuscular junction (NMJ). Here, we review and bring together the previously published data to emphasize the relevance of these receptors for developmental axonal competition, synaptic loss and mature NMJ functional modulation. However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, muscle, and glial cells) cross the extracellular cleft to generate signals in target metabotropic receptors. Thus, the integrated interpretation of the complementary function of all these receptors is needed. We previously studied, in the NMJ, the links of AR with mAChR and the neurotrophin receptor TrkB in the control of synapse elimination and transmitter release. We conclude that AR cooperate with these receptors through synergistic and antagonistic effects in the developmental synapse elimination process. In the adult NMJ, this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors operating normally (i.e., the functional integrity of mAChR depends on AR operating normally). These observations underlie the relevance of AR in the NMJ function.

Adenosine Receptors in Developing and Adult Mouse Neuromuscular Junctions and Functional Links With Other Metabotropic Receptor Pathways

Directory of Open Access Journals (Sweden)

Josep Tomàs

2018-04-01

Full Text Available In the last few years, we have studied the presence and involvement in synaptogenesis and mature transmitter release of the adenosine autoreceptors (AR in the mammalian neuromuscular junction (NMJ. Here, we review and bring together the previously published data to emphasize the relevance of these receptors for developmental axonal competition, synaptic loss and mature NMJ functional modulation. However, in addition to AR, activity-dependent mediators originating from any of the three cells that make the synapse (nerve, muscle, and glial cells cross the extracellular cleft to generate signals in target metabotropic receptors. Thus, the integrated interpretation of the complementary function of all these receptors is needed. We previously studied, in the NMJ, the links of AR with mAChR and the neurotrophin receptor TrkB in the control of synapse elimination and transmitter release. We conclude that AR cooperate with these receptors through synergistic and antagonistic effects in the developmental synapse elimination process. In the adult NMJ, this cooperation is manifested so as that the functional integrity of a given receptor group depends on the other receptors operating normally (i.e., the functional integrity of mAChR depends on AR operating normally. These observations underlie the relevance of AR in the NMJ function.

Characterization of the chicken muscle insulin receptor

International Nuclear Information System (INIS)

Adamo, M.; Simon, J.; Rosebrough, R.W.; McMurtry, J.P.; Steele, N.C.; LeRoith, D.

1987-01-01

Insulin receptors are present in chicken skeletal muscle. Crude membrane preparations demonstrated specific 125 I-insulin binding. The nonspecific binding was high (36-55% of total binding) and slightly lower affinity receptors were found than are typically observed for crude membrane insulin binding in other chicken tissues. Affinity crosslinking of 125 I-insulin to crude membranes revealed insulin receptor alpha-subunits of Mr 128K, intermediate between those of liver (134K) and brain (124K). When solubilized and partially purified on wheat germ agglutinin (WGA) affinity columns, chicken muscle insulin receptors exhibited typical high affinity binding, with approximately 10(-10) M unlabeled insulin producing 50% inhibition of the specific 125 I-insulin binding. WGA purified chicken muscle insulin receptors also exhibited insulin-stimulated autophosphorylation of the beta-subunit, which appeared as phosphorylated bands of 92- and 81K. Both bands were immunoprecipitated by anti-receptor antiserum (B10). WGA purified membranes also demonstrated dose-dependent insulin-stimulated phosphorylation of the exogenous substrate poly(Glu,Tyr)4:1. However, unlike chicken liver, chicken muscle insulin receptor number and tyrosine kinase activity were unaltered by 48 hr of fasting or 48 hr of fasting and 24 hr of refeeding. Thus, despite the presence of insulin receptors in chicken muscle showing normal coupling to receptor tyrosine kinase activity, nutritional alterations modulate these parameters in a tissue-specific manner in chickens

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB{sub 1} cannabinoid receptors

Energy Technology Data Exchange (ETDEWEB)

Jäntti, Maria H., E-mail: maria.jantti@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland); Mandrika, Ilona, E-mail: ilona@biomed.lu.lv [Latvian Biomedical Research and Study Centre, Ratsupites Str. 1, Riga LV 1067 (Latvia); Kukkonen, Jyrki P., E-mail: jyrki.kukkonen@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland)

2014-03-07

Highlights: • OX{sub 1} and OX{sub 2} orexin and CB{sub 1} cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX{sub 1} orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB{sub 1} cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX{sub 1}, OX{sub 2} and CB{sub 1} receptors, C-terminally fused with either Renilla luciferase or GFP{sup 2} green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB{sub 1} receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP{sup 2} to CB{sub 1} produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX{sub 1}–OX{sub 2} interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB{sub 1} receptors, dimerization could be an effective way

Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism

International Nuclear Information System (INIS)

Noble, E.P.; Blum, K.; Ritchie, T.; Montgomery, A.; Sheridan, P.J.

1991-01-01

The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and non-alcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (lambda hD2G1) of the human D2 dopamine receptor gene. The binding characteristics (Kd [binding affinity] and Bmax [number of binding sites]) of the D2 dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kd was significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmax was significantly reduced compared with the Bmax of subjects with the A2 allele. Moreover, a progressively reduced Bmax was found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2 dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism

Effects of a novel bradykinin B1 receptor antagonist and angiotensin II receptor blockade on experimental myocardial infarction in rats.

Directory of Open Access Journals (Sweden)

Dongmei Wu

Full Text Available The aim of the present study was to evaluate the cardiovascular effects of the novel bradykinin B1 receptor antagonist BI-113823 following myocardial infarction (MI and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin II type 1 (AT1 receptor antagonist after MI in rats.Sprague Dawley rats were subjected to permanent occlusion of the left descending coronary artery. Cardiovascular function was determined at 7 days post MI. Treatment with either B1 receptor antagonist (BI-113823 or AT1 receptor antagonist (irbesartan alone or in combination improved post-MI cardiac function as evidenced by attenuation of elevated left ventricular end diastolic pressure (LVEDP; greater first derivative of left ventricular pressure (± dp/dt max, left ventricle ejection fraction, fractional shorting, and better wall motion; as we as reductions in post-MI up-regulation of matrix metalloproteinases 2 (MMP-2 and collagen III. In addition, the cardiac up-regulation of B1 receptor and AT1 receptor mRNA were markedly reduced in animals treated with BI 113823, although bradykinin B2 receptor and angiotensin 1 converting enzyme (ACE1 mRNA expression were not significantly affected by B1 receptor blockade.The present study demonstrates that treatment with the novel B1 receptor antagonist, BI-113823 improves post-MI cardiac function and does not influence the cardiovascular effects of AT1 receptor antagonist following MI.

Vitamin D receptor and estrogen receptor gene polymorphisms in postmenopausal Danish women

DEFF Research Database (Denmark)

Bagger, Y Z; Hassager, C; Heegaard, Anne-Marie

2000-01-01

To investigate the polymorphisms of the vitamin D receptor (VDR) and estrogen receptor (ER) genes in relation to biochemical markers of bone turnover (serum osteocalcin and urinary collagen type I degradation products (CrossLaps), and to study ER genotypes in relation to serum lipoproteins, blood...... pressure, or changes in these parameters after 2 years of hormone replacement therapy (HRT) in 499 Danish postmenopausal women....

G-protein coupling of cannabinoid receptors

International Nuclear Information System (INIS)

Glass, M.

2001-01-01

Full text: Since the cloning of the cannabinoid CB1 and CB2 receptors in the early 1990's extensive research has focused on understanding their signal transduction pathways. While it has been known for sometime that both receptors can couple to intracellular signalling via pertussis toxin sensitive G-proteins (Gi/Go), the specificity and kinetics of these interactions have only recently been elucidated. We have developed an in situ reconstitution approach to investigating receptor-G-protein interactions. This approach involves chaotropic extraction of receptor containing membranes in order to inactivate or remove endogenous G-proteins. Recombinant or isolated brain G-proteins can then be added back to the receptors, and their activation monitored through the binding of [ 35 S]-GTPγS. This technique has been utilised for an extensive study of cannabinoid receptor mediated activation of G-proteins. In these studies we have established that CB1 couples with high affinity to both Gi and Go type G-proteins. In contrast, CB2 couples strongly to Gi, but has a very low affinity for Go. This finding correlated well with the previous findings that while CB1 and CB2 both couple to the inhibition of adenylate cyclase, CB1 but not CB2 could also inhibit calcium channels. We then examined the ability of a range of cannabinoid agonists to activate the Gi and Go via CB1. Conventional receptor theory suggests that a receptor is either active or inactive with regard to a G-protein and that the active receptor activates all relevant G-proteins equally. However, in this study we found that agonists could produce different degrees of activation, depending on which G-protein was present. Further studies have compared the ability of the two endocannabinoids to drive the activation of Gi or Go. These studies show that agonists can induce multiple forms of activated receptor that differ in their ability to catalyse the activation of Gi or Go. The ability of an agonist to drive a receptor

Identification of Hymenolepis diminuta Cysticercoid Larvae in Tribolium castaneum (Coleoptera:Tenebrionidae Beetles from Iran

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Mahsa Sadat Makki

2017-06-01

Full Text Available Background: Hymenolepis diminuta is a cestod of rodents and rarely infects humans. Infection in humans is via ingestion of infected insects. This study was aimed to detect H. diminuta cysticercoids in red flour beetles, Tribolium castaneum, and cockroaches originated from different regions of Iran.Methods: The red flour beetles and cockroaches were collected from local bakeries in five cities including Tehran, Ahvaz, Kazerun, and Sabzevar during 2010–2011. Some beetles and cockroaches were colonized in insectary and adults from F1 generation were fed on H. diminuta eggs. Both laboratory-infected and field-collected samples were dissected and examined for cysticercoids. Detection of H. diminuta DNA in T. castaneum beetles was performed by targeting a partial sequence of Ribosomal gene.Results: Except the beetles from Ahvaz, all specimens were negative for cysticercoid by microscopy. Of the four dissected beetles from Ahvaz, one harbored 12 cysticercoids. Also, 110 (52% of laboratory-infected beetles showed infection with an average of 12–14 larvae. None of the cockroaches was infected. Two beetles from Ahvaz, includ­ing the remainder of the microscopic positive specimen, yielded the expected amplicon in PCR assay. The H. diminuta DNA sequences generated in this study were identical and matched 97–100% with similar sequences from GenBank database.Conclusion: Lack of infection in the majority of beetles may reflect a low rat infestation rate in those areas, alternatively, the examined specimens might not have been the representative samples of the T. castaneum populations.

The repertoire of trace amine G-protein-coupled receptors

DEFF Research Database (Denmark)

Gloriam, David E.; Bjarnadóttir, Thóra K; Yan, Yi-Lin

2005-01-01

eukaryotic species for receptors similar to the mammalian trace amine (TA) receptor subfamily. We identified 18 new receptors in rodents that are orthologous to the previously known TA-receptors. Remarkably, we found 57 receptors (and 40 pseudogenes) of this type in the zebrafish (Danio rerio), while fugu...... (Takifugu rubripes) had only eight receptors (and seven pseudogenes). We mapped 47 of the zebrafish TA-receptors on chromosomes using radiation hybrid panels and meiotic mapping. The results, together with the degree of conservation and phylogenetic relationships displayed among the zebrafish receptors...

A Novel Mechanism of Androgen Receptor Action

National Research Council Canada - National Science Library

Roberts, Jr, Charles T

2006-01-01

.... Specifically, the authors had determined that the androgen receptor controls the expression of the cell-surface receptor for the hormone IGF-1 at the level of translation of the IGF-1 receptor mRNA...

Receptor binding studies of the living heart

International Nuclear Information System (INIS)

Syrota, A.

1988-01-01

Receptors form a class of intrinsic membrane proteins (or glycoproteins) defined by the high affinity and specificity with which they bind ligands. Many receptors are associated directly or indirectly with membrane ion channels that open or close after a conformational change of the receptor induced by the binding of the neurotransmitter. Changes in number and/or affinity of cardiac neurotransmitter receptors have been associated with myocardial ischemia and infarction, congestive heart failure, and cardiomyopathy as well as diabetes or thyroid-induced heart muscle disease. These alterations of cardiac receptors have been demonstrated in vitro on membrane homogenates from samples collected mainly during surgery or postmortem. The disadvantage of these in vitro binding techniques is that receptors lose their natural environment and their relationships with the other components of the tissue

Genomic organization, annotation, and ligand-receptor inferences of chicken chemokines and chemokine receptor genes based on comparative genomics

Directory of Open Access Journals (Sweden)

Sze Sing-Hoi

2005-03-01

Full Text Available Abstract Background Chemokines and their receptors play important roles in host defense, organogenesis, hematopoiesis, and neuronal communication. Forty-two chemokines and 19 cognate receptors have been found in the human genome. Prior to this report, only 11 chicken chemokines and 7 receptors had been reported. The objectives of this study were to systematically identify chicken chemokines and their cognate receptor genes in the chicken genome and to annotate these genes and ligand-receptor binding by a comparative genomics approach. Results Twenty-three chemokine and 14 chemokine receptor genes were identified in the chicken genome. All of the chicken chemokines contained a conserved CC, CXC, CX3C, or XC motif, whereas all the chemokine receptors had seven conserved transmembrane helices, four extracellular domains with a conserved cysteine, and a conserved DRYLAIV sequence in the second intracellular domain. The number of coding exons in these genes and the syntenies are highly conserved between human, mouse, and chicken although the amino acid sequence homologies are generally low between mammalian and chicken chemokines. Chicken genes were named with the systematic nomenclature used in humans and mice based on phylogeny, synteny, and sequence homology. Conclusion The independent nomenclature of chicken chemokines and chemokine receptors suggests that the chicken may have ligand-receptor pairings similar to mammals. All identified chicken chemokines and their cognate receptors were identified in the chicken genome except CCR9, whose ligand was not identified in this study. The organization of these genes suggests that there were a substantial number of these genes present before divergence between aves and mammals and more gene duplications of CC, CXC, CCR, and CXCR subfamilies in mammals than in aves after the divergence.

The AT2 Receptor and Inflammation

DEFF Research Database (Denmark)

Esquitino, Veronica Valero; Danyel, Leon Alexander; Steckelings, Ulrike M.

2015-01-01

This chapter summarizes current knowledge about the role of the angiotensin type 2 (AT2) receptor in inflammation. The first section provides an overview about molecular mechanisms underlying the anti-inflammatory action of the AT2 receptor. This section is followed...... by a review of the existing literature addressing the role of the AT2 receptor in a wide range of disorders, in which acute or chronic inflammation is an essential contributor to the pathology. These disorders comprise cardiovascular, cerebrovascular, renal, and autoimmune diseases.Taken as a whole......, the vast majority of data support an anti-inflammatory and immunomodulatory role of the AT2 receptor. In light of the current development of AT2 receptor agonists as future drugs for clinical use, diseases with a marked inflammatory component may become a major area of therapeutic use...

NCS-1 associates with adenosine A2A receptors and modulates receptor function

Directory of Open Access Journals (Sweden)

Gemma eNavarro

2012-04-01

Full Text Available Modulation of G protein-coupled receptor (GPCR signalling by local changes in intracellular calcium concentration is an established function of Calmodulin which is known to interact with many GPCRs. Less is known about the functional role of the closely related neuronal EF-hand Ca2+-sensor proteins that frequently associate with calmodulin targets with different functional outcome. In the present study we aimed to investigate if a target of calmodulin – the A2A adenosine receptor, is able to associate with two other neuronal calcium binding proteins, namely NCS-1 and caldendrin. Using bioluminescence resonance energy transfer and co-immunoprecipitation experiments we show the existence of A2A - NCS-1 complexes in living cells whereas caldendrin did not associate with A2A receptors under the conditions tested. Interestingly, NCS-1 binding modulated downstream A2A receptor intracellular signalling in a Ca2+-dependent manner. Taken together this study provides further evidence that neuronal Ca2+-sensor proteins play an important role in modulation of GPCR signalling.

The prostaglandin EP1 receptor potentiates kainate receptor activation via a protein kinase C pathway and exacerbates status epilepticus

Science.gov (United States)

Rojas, Asheebo; Gueorguieva, Paoula; Lelutiu, Nadia; Quan, Yi; Shaw, Renee; Dingledine, Raymond

2014-01-01

Prostaglandin E2 (PGE2) regulates membrane excitability, synaptic transmission, plasticity, and neuronal survival. The consequences of PGE2 release following seizures has been the subject of much study. Here we demonstrate that the prostaglandin E2 receptor 1 (EP1, or Ptger1) modulates native kainate receptors, a family of ionotropic glutamate receptors widely expressed throughout the central nervous system. Global ablation of the EP1 gene in mice (EP1-KO) had no effect on seizure threshold after kainate injection but reduced the likelihood to enter status epilepticus. EP1-KO mice that did experience typical status epilepticus had reduced hippocampal neurodegeneration and a blunted inflammatory response. Further studies with native prostanoid and kainate receptors in cultured cortical neurons, as well as with recombinant prostanoid and kainate receptors expressed in Xenopus oocytes, demonstrated that EP1 receptor activation potentiates heteromeric but not homomeric kainate receptors via a second messenger cascade involving phospholipase C, calcium and protein kinase C. Three critical GluK5 C-terminal serines underlie the potentiation of the GluK2/GluK5 receptor by EP1 activation. Taken together, these results indicate that EP1 receptor activation during seizures, through a protein kinase C pathway, increases the probability of kainic acid induced status epilepticus, and independently promotes hippocampal neurodegeneration and a broad inflammatory response. PMID:24952362

Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1

NARCIS (Netherlands)

Zwijsen, R.M.L.; Buckle, R.S.; Hijmans, E.M.; Loomans, C.J.M.; Bernards, R.A.

1998-01-01

The estrogen receptor (ER) is an important regulator of growth and differentiation of breast epithelium. Transactivation by ER depends on a leucine-rich motif, which constitutes a ligand-regulated binding site for steroid receptor coactivators (SRCs). Cyclin D1 is frequently amplified in breast

Unsaturated free fatty acids increase benzodiazepine receptor agonist binding depending on the subunit composition of the GABAA receptor complex.

Science.gov (United States)

Witt, M R; Westh-Hansen, S E; Rasmussen, P B; Hastrup, S; Nielsen, M

1996-11-01

It has been shown previously that unsaturated free fatty acids (FFAs) strongly enhance the binding of agonist benzodiazepine receptor ligands and GABAA receptor ligands in the CNS in vitro. To investigate the selectivity of this effect, recombinant human GABAA/benzodiazepine receptor complexes formed by different subunit compositions (alpha x beta y gamma 2, x = 1, 2, 3, and 5; y = 1, 2, and 3) were expressed using the baculovirus-transfected Sf9 insect cell system. At 10(-4) M, unsaturated FFAs, particularly arachidonic (20:4) and docosahexaenoic (22:6) acids, strongly stimulated (> 200% of control values) the binding of [3H]flunitrazepam ([3H]FNM) to the alpha 3 beta 2 gamma 2 receptor combination in whole cell preparations. No effect or small increases in levels of unsaturated FFAs on [3H]FNM binding to alpha 1 beta x gamma 2 and alpha 2 beta x gamma 2 receptor combinations were observed, and weak effects (130% of control values) were detected using the alpha 5 beta 2 gamma 2 receptor combination. The saturated FFAs, stearic and palmitic acids, were without effect on [3H]FNM binding to any combination of receptor complexes. The hydroxylated unsaturated FFAs, ricinoleic and ricinelaidic acids, were shown to decrease the binding of [3H]FNM only if an alpha 1 beta 2 gamma 2 receptor combination was used. Given the heterogeneity of the GABAA/ benzodiazepine receptor subunit distribution in the CNS, the effects of FFAs on the benzodiazepine receptor can be assumed to vary at both cellular and regional levels.

Effects of histamine H1 receptor signaling on glucocorticoid receptor activity. Role of canonical and non-canonical pathways

NARCIS (Netherlands)

Zappia, C.D.; Granja-Galeano, G.; Fernández, N.; Shayo, C.; Davio, C.; Fitzsimons, C.P.; Monczor, F.

2015-01-01

Histamine H1 receptor (H1R) antagonists and glucocorticoid receptor (GR) agonists are used to treat inflammatory conditions such as allergic rhinitis, atopic dermatitis and asthma. Consistent with the high morbidity levels of such inflammatory conditions, these receptors are the targets of a vast

Purification of family B G protein-coupled receptors using nanodiscs: Application to human glucagon-like peptide-1 receptor.

Directory of Open Access Journals (Sweden)

Yingying Cai

Full Text Available Family B G protein-coupled receptors (GPCRs play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1 receptor (GLP1R, whose agonists, e.g. exendin-4, are used for the treatment of type 2 diabetes mellitus. The receptor was expressed in HEK293S GnTl- cells using our recently developed protocol. The protocol incorporates the receptor into the native-like lipid environment of reconstituted high density lipoprotein (rHDL particles, also known as nanodiscs, immediately after the membrane solubilization step followed by chromatographic purification, minimizing detergent contact with the target receptor to reduce denaturation and prolonging stabilization of receptor in lipid bilayers without extra steps of reconstitution. This method yielded purified GLP1R in nanodiscs that could bind to GLP-1 and exendin-4 and activate Gs protein. This nanodisc purification method can potentially be a general strategy to routinely obtain purified family B GPCRs in the 10s of microgram amounts useful for spectroscopic analysis of receptor functions and activation mechanisms.

Purification of family B G protein-coupled receptors using nanodiscs: Application to human glucagon-like peptide-1 receptor.

Science.gov (United States)

Cai, Yingying; Liu, Yuting; Culhane, Kelly J; DeVree, Brian T; Yang, Yang; Sunahara, Roger K; Yan, Elsa C Y

2017-01-01

Family B G protein-coupled receptors (GPCRs) play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), whose agonists, e.g. exendin-4, are used for the treatment of type 2 diabetes mellitus. The receptor was expressed in HEK293S GnTl- cells using our recently developed protocol. The protocol incorporates the receptor into the native-like lipid environment of reconstituted high density lipoprotein (rHDL) particles, also known as nanodiscs, immediately after the membrane solubilization step followed by chromatographic purification, minimizing detergent contact with the target receptor to reduce denaturation and prolonging stabilization of receptor in lipid bilayers without extra steps of reconstitution. This method yielded purified GLP1R in nanodiscs that could bind to GLP-1 and exendin-4 and activate Gs protein. This nanodisc purification method can potentially be a general strategy to routinely obtain purified family B GPCRs in the 10s of microgram amounts useful for spectroscopic analysis of receptor functions and activation mechanisms.

Ror receptor tyrosine kinases: orphans no more

OpenAIRE

Green, Jennifer L.; Kuntz, Steven G.; Sternberg, Paul W.

2008-01-01

Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either act...

Studies on insulin receptor, 2

International Nuclear Information System (INIS)

Sakai, Yukio

1979-01-01

The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using 125 I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and 125 I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia. (author)

Membrane Trafficking of Death Receptors: Implications on Signalling

Directory of Open Access Journals (Sweden)

Wulf Schneider-Brachert

2013-07-01

Full Text Available Death receptors were initially recognised as potent inducers of apoptotic cell death and soon ambitious attempts were made to exploit selective ignition of controlled cellular suicide as therapeutic strategy in malignant diseases. However, the complexity of death receptor signalling has increased substantially during recent years. Beyond activation of the apoptotic cascade, involvement in a variety of cellular processes including inflammation, proliferation and immune response was recognised. Mechanistically, these findings raised the question how multipurpose receptors can ensure selective activation of a particular pathway. A growing body of evidence points to an elegant spatiotemporal regulation of composition and assembly of the receptor-associated signalling complex. Upon ligand binding, receptor recruitment in specialized membrane compartments, formation of receptor-ligand clusters and internalisation processes constitute key regulatory elements. In this review, we will summarise the current concepts of death receptor trafficking and its implications on receptor-associated signalling events.

Are olfactory receptors really olfactive?

DEFF Research Database (Denmark)

Giorgi, Franco; Maggio, Roberto; Bruni, Luis Emilio

2011-01-01

environmental conditions. By adopting this standpoint, the functional attribution as olfactory or chemotactic sensors to these receptors should not be seen neither as a cause conditioning receptor gene expression, nor as a final effect resulting from genetically predetermined programs, but as a direct...... and odor-decoding processes. However, this type of explanation does not entirely justify the role olfactory receptors have played during evolution, since they are also expressed ectopically in different organs and/or tissues. Homologous olfactory genes have in fact been found in such diverse cells and....../or organs as spermatozoa, testis and kidney where they are assumed to act as chemotactic sensors or renin modulators. To justify their functional diversity, homologous olfactory receptors are assumed to share the same basic role: that of conferring a self-identity to cells or tissues under varying...

Symposium overview: alterations in cytokine receptors by xenobiotics.

Science.gov (United States)

Cohen, M D; Schook, L B; Oppenheim, J J; Freed, B M; Rodgers, K E

1999-04-01

A symposium entitled Alterations in Cytokine Receptors by Xenobiotics was held at the 37th Annual Meeting of the Society of Toxicology (SOT) in Seattle, Washington. The symposium was sponsored by the Immunotoxicology Specialty Section of SOT and was designed to present information on the effect of several different classes of xenobiotics on various aspects of receptor function (i.e., post-receptor signal transduction of receptor expression), or the involvement of cytokine receptors in the action of the toxicant under consideration. This symposium brought together scientists in the area of receptor immunobiology whose expertise in receptor modulation encompassed those major signaling agents involved in the normal immune response, i.e., proinflammatory cytokines, chemokines, interleukins, and interferons. The following is a summary of each of the individual presentations.

Group III mGlu receptor agonists potentiate the anticonvulsant effect of AMPA and NMDA receptor block.

Science.gov (United States)

De Sarro, Giovambattista; Chimirri, Alba; Meldrum, Brian S

2002-09-06

We report the anticonvulsant action in DBA/2 mice of two mGlu Group III receptor agonists: (R,S)-4-phosphonophenylglycine, (R,S)-PPG, a compound with moderate mGlu8 selectivity, and of (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid, ACPT-1, a selective agonist for mGlu4alpha receptors. Both compounds, given intracerebroventricularly at doses which did not show marked anticonvulsant activity, produced a consistent shift to the left of the dose-response curves (i.e. enhanced the anticonvulsant properties) of 1-(4'-aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin-4-one hydrochloride, CFM-2, a noncompetitive AMPA receptor antagonist, and 3-((+/-)-2-carboxypiperazin-4-yl)-1-phosphonic acid, CPPene, a competitive NMDA receptor antagonist, in DBA/2 mice. In addition, (R,S)-PPG and ACPT-1 administered intracerebroventricularly prolonged the time course of the anticonvulsant properties of CFM-2 (33 micromol/kg, i.p.) and CPPene (3.3 micromol/kg, i.p.) administered intraperitoneally. We conclude that modest reduction of synaptic glutamate release by activation of Group III metabotropic receptors potentiates the anticonvulsant effect of AMPA and NMDA receptor blockade. Copyright 2002 Elsevier Science B.V.

Psychopharmacology of 5-HT1A receptors

International Nuclear Information System (INIS)

Cowen, Philip J.

2000-01-01

Serotonin 1A (5-HT 1A ) receptors are located on both 5-HT cell bodies where they act as inhibitory autoreceptors and at postsynaptic sites where they mediate the effects of 5-HT released from nerve terminals. The sensitivity of 5-HT 1A receptors in humans can be measured using the technique of pharmacological challenge. For example, acute administration of a selective 5-HT 1A receptor agonist, such as ipsapirone, decreases body temperature and increases plasma cortisol through activation of pre- and postsynaptic 5-HT 1A receptors, respectively. Use of this technique has demonstrated that unmedicated patients with major depression have decreased sensitivity of both pre- and postsynaptic 5-HT 1A receptors. Treatment with selective serotonin reuptake inhibitors further down-regulates 5-HT 1A receptor activity. Due to the hypotheses linking decreased sensitivity of 5-HT 1A autoreceptors with the onset of antidepressant activity, there is current interest in the therapeutic efficacy of combined treatment with selective serotonin reuptake inhibitors and 5-HT 1A receptor antagonists

Characteristic molecular vibrations of adenosine receptor ligands.

Science.gov (United States)

Chee, Hyun Keun; Yang, Jin-San; Joung, Je-Gun; Zhang, Byoung-Tak; Oh, S June

2015-02-13

Although the regulation of membrane receptor activation is known to be crucial for molecular signal transduction, the molecular mechanism underlying receptor activation is not fully elucidated. Here we study the physicochemical nature of membrane receptor behavior by investigating the characteristic molecular vibrations of receptor ligands using computational chemistry and informatics methods. By using information gain, t-tests, and support vector machines, we have identified highly informative features of adenosine receptor (AdoR) ligand and corresponding functional amino acid residues such as Asn (6.55) of AdoR that has informative significance and is indispensable for ligand recognition of AdoRs. These findings may provide new perspectives and insights into the fundamental mechanism of class A G protein-coupled receptor activation. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Neurobeachin regulates neurotransmitter receptor trafficking to synapses

NARCIS (Netherlands)

Nair, R.; Lauks, J.; Jung, S; Cooke, N.E.; de Wit, H.; Brose, N.; Kilimann, M.W.; Verhage, M.; Rhee, J.

2013-01-01

The surface density of neurotransmitter receptors at synapses is a key determinant of synaptic efficacy. Synaptic receptor accumulation is regulated by the transport, postsynaptic anchoring, and turnover of receptors, involving multiple trafficking, sorting, motor, and scaffold proteins. We found

Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors.

Science.gov (United States)

Khan, Muhammad Zahid; He, Ling

2017-04-01

In the central nervous system (CNS), G protein-coupled receptors (GPCRs) are the most fruitful targets for neuropsychopharmacological drug development. Rhodopsin (class A) is the most studied class of GPCR and includes orphan receptors for which the endogenous ligand is not known or is unclear. Characterization of orphan GPCRs has proven to be challenging, and the production pace of GPCR-based drugs has been incredibly slow. Determination of the functions of these receptors may provide unexpected insight into physiological and neuropathological processes. Advances in various methods and techniques to investigate orphan receptors including in situ hybridization and knockdown/knockout (KD/KO) showed extensive expression of these receptors in the mammalian brain and unmasked their physiological and neuropathological roles. Due to these rapid progress and development, orphan GPCRs are rising as a new and promising class of drug targets for neurodegenerative diseases and psychiatric disorders. This review presents a neuropsychopharmacological perspective of 26 orphan receptors of rhodopsin (class A) family, namely GPR3, GPR6, GPR12, GPR17, GPR26, GPR35, GPR39, GPR48, GPR49, GPR50, GPR52, GPR55, GPR61, GPR62, GPR63, GPR68, GPR75, GPR78, GPR83, GPR84, GPR85, GPR88, GPR153, GPR162, GPR171, and TAAR6. We discussed the expression of these receptors in mammalian brain and their physiological roles. Furthermore, we have briefly highlighted their roles in neurodegenerative diseases and psychiatric disorders including Alzheimer's disease, Parkinson's disease, neuroinflammation, inflammatory pain, bipolar and schizophrenic disorders, epilepsy, anxiety, and depression.

Desensitization of γ-aminobutyric acid receptor from rat brain: two distinguishable receptors on the same membrane

International Nuclear Information System (INIS)

Cash, D.J.; Subbarao, K.

1987-01-01

Transmembrane chloride flux mediated by γ-aminobutyric acid (GABA) receptor can be measured with a mammalian brain homogenate preparation containing sealed membrane vesicles. The preparation can be mixed rapidly with solutions of defined composition. Influx of 36 Cl - tracer initiated by mixing with GABA was rapidly terminated by mixing with bicuculline methiodide. The decrease in the isotope influx measurement due to prior incubation of the vesicle preparation with GABA, which increased with preincubation time and GABA concentration, was attributed to desensitization of the GABA receptor. By varying the time of preincubation with GABA between 10 ms and 50 s with quench-flow technique, the desensitization rates could be measured over their whole time course independently of the chloride ion flux rate. Most of the receptor activity decreased in a fast phase of desensitization complete in 200 ms at saturation with GABA. Remaining activity was desensitized in a few seconds. These two phases of desensitization were each kinetically first order and were shown to correspond with two distinguishable GABA receptors on the same membrane. The receptor activities could be estimated, and the faster desensitizing receptor was the predominant one, giving on average ca. 80% of the total activity. The half-response concentrations were similar, 150 and 114 μM for the major and minor receptors, respectively. The dependence on GABA concentration indicated that desensitization is mediated by two GABA binding sites. The fast desensitization rate was approximately 20-fold faster than previously reported rates while the slower desensitization rate was slightly faster than previously reported rates

Behavioral analysis of Drosophila transformants expressing human taste receptor genes in the gustatory receptor neurons.

Science.gov (United States)

Adachi, Ryota; Sasaki, Yuko; Morita, Hiromi; Komai, Michio; Shirakawa, Hitoshi; Goto, Tomoko; Furuyama, Akira; Isono, Kunio

2012-06-01

Transgenic Drosophila expressing human T2R4 and T2R38 bitter-taste receptors or PKD2L1 sour-taste receptor in the fly gustatory receptor neurons and other tissues were prepared using conventional Gal4/UAS binary system. Molecular analysis showed that the transgene mRNAs are expressed according to the tissue specificity of the Gal4 drivers. Transformants expressing the transgene taste receptors in the fly taste neurons were then studied by a behavioral assay to analyze whether transgene chemoreceptors are functional and coupled to the cell response. Since wild-type flies show strong aversion against the T2R ligands as in mammals, the authors analyzed the transformants where the transgenes are expressed in the fly sugar receptor neurons so that they promote feeding ligand-dependently if they are functional and activate the neurons. Although the feeding preference varied considerably among different strains and individuals, statistical analysis using large numbers of transformants indicated that transformants expressing T2R4 showed a small but significant increase in the preference for denatonium and quinine, the T2R4 ligands, as compared to the control flies, whereas transformants expressing T2R38 did not. Similarly, transformants expressing T2R38 and PKD2L1 also showed a similar preference increase for T2R38-specific ligand phenylthiocarbamide (PTC) and a sour-taste ligand, citric acid, respectively. Taken together, the transformants expressing mammalian taste receptors showed a small but significant increase in the feeding preference that is taste receptor and also ligand dependent. Although future improvements are required to attain performance comparable to the endogenous robust response, Drosophila taste neurons may serve as a potential in vivo heterologous expression system for analyzing chemoreceptor function.

Development of antibodies against the rat brain somatostatin receptor.

Science.gov (United States)

Theveniau, M; Rens-Domiano, S; Law, S F; Rougon, G; Reisine, T

1992-05-15

Somatostatin (SRIF) is a neurotransmitter in the brain involved in the regulation of motor activity and cognition. It induces its physiological actions by interacting with receptors. We have developed antibodies against the receptor to investigate its structural properties. Rabbit polyclonal antibodies were generated against the rat brain SRIF receptor. These antibodies (F4) were able to immunoprecipitate solubilized SRIF receptors from rat brain and the cell line AtT-20. The specificity of the interaction of these antibodies with SRIF receptors was further demonstrated by immunoblotting. F4 detected SRIF receptors of 60 kDa from rat brain and adrenal cortex and the cell lines AtT-20, GH3, and NG-108, which express high densities of SRIF receptors. They did not detect immunoreactive material from rat liver or COS-1, HEPG, or CRL cells, which do not express functional SRIF receptors. In rat brain, 60-kDa immunoreactivity was detected by F4 in the hippocampus, cerebral cortex, and striatum, which have high densities of SRIF receptors. However, F4 did not interact with proteins from cerebellum and brain stem, which express few SRIF receptors. Immunoreactive material cannot be detected in rat pancreas or pituitary, which have been reported to express a 90-kDa SRIF receptor subtype. The selective detection of 60-kDa SRIF receptors by F4 indicates that the 60- and 90-kDa SRIF receptor subtypes are immunologically distinct. The availability of antibodies that selectively detect native and denatured brain SRIF receptors provides us with a feasible approach to clone the brain SRIF receptor gene(s).

Evolution of endothelin receptors in vertebrates.

Science.gov (United States)

Braasch, Ingo; Schartl, Manfred

2014-12-01

Endothelin receptors are G protein coupled receptors (GPCRs) of the β-group of rhodopsin receptors that bind to endothelin ligands, which are 21 amino acid long peptides derived from longer prepro-endothelin precursors. The most basal Ednr-like GPCR is found outside vertebrates in the cephalochordate amphioxus, but endothelin ligands are only present among vertebrates, including the lineages of jawless vertebrates (lampreys and hagfishes), cartilaginous vertebrates (sharks, rays, and chimaeras), and bony vertebrates (ray-finned fishes and lobe-finned vertebrates including tetrapods). A bona fide endothelin system is thus a vertebrate-specific innovation with important roles for regulating the cardiovascular system, renal and pulmonary processes, as well as for the development of the vertebrate-specific neural crest cell population and its derivatives. Expectedly, dysregulation of endothelin receptors and the endothelin system leads to a multitude of human diseases. Despite the importance of different types of endothelin receptors for vertebrate development and physiology, current knowledge on endothelin ligand-receptor interactions, on the expression of endothelin receptors and their ligands, and on the functional roles of the endothelin system for embryonic development and in adult vertebrates is very much biased towards amniote vertebrates. Recent analyses from a variety of vertebrate lineages, however, have shown that the endothelin system in lineages such as teleost fish and lampreys is more diverse and is divergent from the mammalian endothelin system. This diversity is mainly based on differential evolution of numerous endothelin system components among vertebrate lineages generated by two rounds of whole genome duplication (three in teleosts) during vertebrate evolution. Here we review current understanding of the evolutionary history of the endothelin receptor family in vertebrates supplemented with surveys on the endothelin receptor gene complement of

TLX: An elusive receptor.

Science.gov (United States)

Benod, Cindy; Villagomez, Rosa; Webb, Paul

2016-03-01

TLX (tailless receptor) is a member of the nuclear receptor superfamily and belongs to a class of nuclear receptors for which no endogenous or synthetic ligands have yet been identified. TLX is a promising therapeutic target in neurological disorders and brain tumors. Thus, regulatory ligands for TLX need to be identified to complete the validation of TLX as a useful target and would serve as chemical probes to pursue the study of this receptor in disease models. It has recently been proved that TLX is druggable. However, to identify potent and specific TLX ligands with desirable biological activity, a deeper understanding of where ligands bind, how they alter TLX conformation and of the mechanism by which TLX mediates the transcription of its target genes is needed. While TLX is in the process of escaping from orphanhood, future ligand design needs to progress in parallel with improved understanding of (i) the binding cavity or surfaces to target with small molecules on the TLX ligand binding domain and (ii) the nature of the TLX coregulators in particular cell and disease contexts. Both of these topics are discussed in this review. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rapid resensitization of purinergic receptor function in human platelets.

Science.gov (United States)

Mundell, S J; Barton, J F; Mayo-Martin, M B; Hardy, A R; Poole, A W

2008-08-01

Adenosine diphosphate (ADP) is a critical regulator of platelet activation, mediating its actions through two G protein-coupled receptors (GPCRs), the P2Y(1) and P2Y(12) purinergic receptors. Recently, we demonstrated that both receptors desensitize and internalize in human platelets by differential kinase-dependent mechanisms. To demonstrate whether responses to P2Y(1) and P2Y(12) purinergic receptors resensitize in human platelets and determine the role of receptor traffic in this process. These studies were undertaken either in human platelets or in cells stably expressing epitope-tagged P2Y(1) and P2Y(12) purinergic receptor constructs. In this study we show for the first time that responses to both of these receptors can rapidly resensitize following agonist-dependent desensitization in human platelets. Further, we show that in human platelets or in 1321N1 cells stably expressing receptor constructs, the disruption of receptor internalization, dephosphorylation or subsequent receptor recycling is sufficient to block resensitization of purinergic receptor responses. We also show that, in platelets, internalization of both these receptors is dependent upon dynamin, and that this process is required for resensitization of responses. This study is therefore the first to show that both P2Y(1) and P2Y(12) receptor activities are rapidly and reversibly modulated in human platelets, and it reveals that the underlying mechanism requires receptor trafficking as an essential part of this process.

The MC4 receptor and control of appetite

NARCIS (Netherlands)

Adan, R. A. H.; Tiesjema, B.; Hillebrand, J. J. G.; La Fleur, S. E.; Kas, M. J. H.; de Krom, M.

2006-01-01

Mutations in the human melanocortin (MC)4 receptor have been associated with obesity, which underscores the relevance of this receptor as a drug target to treat obesity. Infusion of MC4R agonists decreases food intake, whereas inhibition of MC receptor activity by infusion of an MC receptor

A new family of insect tyramine receptors

DEFF Research Database (Denmark)

Cazzamali, Giuseppe; Klærke, Dan Arne; Grimmelikhuijzen, Cornelis J P

2005-01-01

in the genomic databases from the malaria mosquito Anopheles gambiae and the honeybee Apis mellifera. These four tyramine or tyramine-like receptors constitute a new receptor family that is phylogenetically distinct from the previously identified insect octopamine/tyramine receptors. The Drosophila tyramine...

Receptor conversion in distant breast cancer metastases