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PubMed2001

Concentrations and patterns of organochlorine contaminants in white whales (Delphinapterus leucas) from Svalbard, Norway.

Blubber was collected from live-captured, adult male white whales (Delphinapterus leucas) from Svalbard, Norway, and analysed for levels and patterns of organochlorine (OC) contaminants. The OC compounds analysed were HCB, dieldrin, sigmaHCH (alpha-HCH, beta-HCH and gamma-HCH), sigmaChl (heptachlor epoxide, oxychlordane, cis-chlordane, trans-nonachlor, and cis-nonachlor), sigmaDDT (pp'-DDT, pp'-DDE and pp'-DDD) and sigmaPCB (27 PCB congeners). The major OC compounds detected in the blubber were sigmaPCB (5103+/-1874 ng/g l.w.) and sigmaDDT (5108+/-1089 ng/g l.w.), which made up 70% of the sigmaOC. These compounds were followed in prevalence by sigmaChl (2872+/-1177 ng/g l.w.), which contributed 20% of the sigmaOC burden. SigmaHCH, HCB and dieldrin were present, but at low concentrations. This OC pattern is typical of top predators in Arctic marine food chains. OC levels in white whales from Svalbard are lower than white whales from the St Lawrence River in Canada and are generally similar to values reported previously for other Arctic white whale stocks. Some geographic patterns in relative prevalence of various OC compounds appear to be quite consistent among various marine mammal species in the Arctic. PCB and DDT concentrations in Svalbard's white whales are below the levels that are thought to have negative effects on reproduction or the immune system.

Adipose Tissue↗
PubMed2001

Organochlorine pesticide, polychlorinated biphenyl and heavy metal concentrations in wolves (Canis lupus L. 1758) from north-west Russia.

The wolf Canis lupus is a major terrestrial predator in eastern Europe and, as a top carnivore, may be exposed to high concentrations of contaminants that are readily transferred through the food chain. Despite this, there are few published data on pollutant and pesticide levels in wolves. This study utilised tissues from animals legally killed by hunters for other reasons (animals were not killed for the purposes of this study) to carry out the only detailed investigation of contaminants in wolves in Europe and the first in animals from Eastern Europe. The livers of 58 wolves from the Tver and Smoliensk regions of northwest Russia (54 degrees N 31 degrees E to 57 degrees N 35 degrees E) were analysed for seven organochlorine pesticides, 24 PCB congeners, Aroclor 1254-matched summed PCBs (sigmaPCBs), total mercury, cadmium and lead. Cadmium, most of the organochlorine pesticides and many PCB congeners were not detectable in any of the wolves. Hexachlorobenzene, alpha-HCH, pp'DDE, PCB congeners 118, 138, 149 and 156 and lead were detected in up to 6% of livers. Dieldrin, PCB congeners 153, 170 and 180, sigmaPCBs and mercury were detected more frequently. Contaminant levels were generally low; maximum wet weight concentrations of any of the organochlorine pesticides, sigmaPCBs and mercury were less than 0.1, 1 and 0.25 microg g(-1), respectively. PCB congeners 153, 170 and 180 accounted for 41% of the sigmaPCBs. Dieldrin, sigmaPCBs and mercury concentrations did not vary significantly between males and females nor between adult and juvenile (< 12 months old) wolves apart from the sigmaPCB concentration, which was on average five times higher in adults than juveniles. Liver residues were generally below the level normally associated with adverse effects except for lead levels which exceeded the critical 5 microg g(-1) dry wt. concentration in three of the 58 animals examined.

Age Factors↗
PubMed2002

Burden of organochlorine pesticides in blood and its effect on thyroid hormones in women.

Man has utilized a wide variety of pesticides to combat the crop pests and vectors of human diseases. However, in this process, he has overlooked the darker side of these noxious chemicals, the concentrations of which have reached the environment and pose serious threats, such as mutagenesis, teratogenesis, carcinogenesis and endocrine dysfunction in various components of the ecosystem. The present study was planned to assess the burden of organochlorine pesticides and their influence on thyroid function in women. The study included a total of 123 women from Jaipur City who visited the Thyroid clinic in SMS Medical College and Hospital. One hundred women showed normal thyroid hormone levels while the remaining 23 women had depleted T4 and high TSH levels. The qualitative and quantitative estimation of organochlorine pesticides was carried out by gas chromatography. Out of the analyzed pesticides, the concentration of p,p'-DDT and its metabolites was higher in all the subjects, but dieldrin was found to be significantly high in the hypothyroid women. The correlation analysis for dieldrin and depleted T4 levels in hypothyroid women elicited an inverse relationship between them.

Adult↗
PubMed2000

Temporal and spatial trends of persistent organochlorines in Greenland walrus (Odobenus rosmarus rosmarus).

Persistent organochlorines [PCBs, DDT and chlordane related compounds, dieldrin, toxaphene, hexachlorocyclohexane (HCH), chlorobenzenes] were determined in blubber of Atlantic walrus (Odobenus rosmarus rosmarus) in 1978 and 1988 from the Avanersuaq (Thule) region of north-west Greenland and in 1989 from Ittoqqortoormiit (Scoresbysund) in east Greenland. Lowest concentrations of organochlorines (OCs) were found in the samples from the Avanersuaq region while much higher levels of all compounds, except HCH isomers and mono/dichlorobiphenyls (CB5/8), were observed in samples (all males) from Ittoqqortoormiit. Total PCBs (sigma PCB) averaged 246 ng/g (wet wt.) male walrus from Avanersuaq and 2860 ng/g in samples from Ittoqqortoormiit. DDT isomers showed the greatest difference between the two locations, 50 x for p,p'-DDE and 69 x higher for p,p'-DDT. Ittoqqortoormiit walrus showed the pattern of OCs characteristic of seal-eating animals although the consumption of other organisms cannot be ruled out. The higher levels of OCs in east Greenland compared to north-west Greenland animals were consistent with results for polar bears, seals and gulls from the same regions. Principal components analysis showed that the pattern of OCs in Ittoqqortoormiit walrus was very similar to that in walrus from Inukjuaq in east Hudson Bay, which have previously been reported to be seal eaters, and quite distinct from the Avanersuaq walrus. No significant differences in mean concentrations of any OCs were found between male walrus from 1978 and 1988. For females, there were significantly higher levels of CB5/8, trichlorobiphenyls, dieldrin, toxaphene and alpha HCH as well as sigma HCH but not for sigma PCBs or DDT compounds. The data for Greenland walrus from the 1970s and late 1980s provide a baseline for future trend monitoring in walrus.

Adipose Tissue↗
PubMed2003

Fipronil modulation of glutamate-induced chloride currents in cockroach thoracic ganglion neurons.

Fipronil is the first phenylpyrazole insecticide introduced for pest control. It is effective against some insects that have become resistant to other insecticides, and exhibits low mammalian toxicity. Although fipronil is known to block GABA receptors, the mechanisms of its selective toxicity and efficacy against insects with dieldrin-resistant GABA receptors are not fully understood. We studied the effects of fipronil on the inhibitory glutamate receptor-chloride channel complex, which is found only in invertebrates. Glutamate-activated chloride currents were recorded from neurons isolated from cockroach thoracic ganglia using the whole-cell patch clamp technique. When glutamate was applied to a neuron, it evoked inward currents with an EC50 of 36.8 +/- 3.0 microM and a Hill coefficient of 1.56 +/- 0.17. The similarity between the reversal potential and the calculated chloride equilibrium potential indicated that glutamate-induced currents were carried by chloride ions. Fipronil suppressed the glutamate-induced peak currents in a dose-dependent manner with an IC50 of 0.73 +/- 0.27 microM and a Hill coefficient of 0.68 +/- 0.15. The current decay phases were greatly prolonged after fipronil application in a concentration-dependent manner. Picrotoxinin (PTX) at 100 microM slightly suppressed glutamate-induced currents to 87.8 +/- 3.7% of the control, and dieldrin at 100 microM had no effect (96.7 +/- 3.1%). AP5 and CNQX, mammalian glutamate receptor antagonists, were without effect on glutamate-induced Cl- currents. It is concluded that the potent blocking action of fipronil against glutamate-gated chloride channels may contribute to the higher toxicity against insects than mammals, as well as the efficacy against insects resistant to other insecticides.

Animals↗
PubMed1997

Organochlorine pesticides in pasteurized milk and associated health risks.

The presence of organochlorine pesticides (alpha-HCH, beta-HCH, lindane, aldrin, dieldrin, heptachlor, heptachlor epoxide, chlordane and the isomers and metabolites of DDT) in Spanish pasteurized milk were investigated. 95% of the samples contained one of the isomers of the HCH group and 12.9% of them exceeded the maximum residue limit permitted by the European Union; six samples went over that limit for heptachlor epoxide and 74.63% of the samples contained chlordane at higher concentrations than those permitted by the legislation. None of the samples exceeded the limit for the DDT group. The mean concentrations detected for each pesticide were as follows (mg/kg): alpha-HCH = 0.015; beta-HCH = 0.039; lindane = 0.007; delta-HCH = 0.07; aldrin = 0.002; dieldrin = 0.028; chlordane = 0.101; heptachlor = 0.011; heptachlor epoxide = 0.021; o.p'-DDD = 0.016; p.p'-DDD = 0.009; p.p'-DDE = 0.045 (DDT + metabolites = 0.067).

Animals↗
PubMed2002

Assessing the estrogenic potential of organochlorine pesticides in primary cultures of male rainbow trout (Oncorhynchus mykiss) hepatocytes using vitellogenin as a biomarker.

Many organochlorine pesticides are suspected of impairing natural hormonal function in organisms by mimicking endogenous estrogen. The aim of this study was to assess the estrogenic activity of the organochlorine pesticides o,p'-DDT, dieldrin, aldrin, heptachlor, mirex and DDT in rainbow trout hepatocyte cultures using vitellogenin (Vtg) as the biomarker. A wide range of pesticide concentrations (0.0001-100 microM) was evaluated. Among the pesticides tested, o,p'-DDT was the most potent inducer of Vtg. The lower potency of technical grade DDT relative to o,p'-DDT could be explained by the fact that this pesticide is a mixture of two different pesticides (18% o,p'-DDT and 77% p,p'-DDT). This suggests that o,p'-DDT is a stronger inducer of Vtg than p,p'-DDT. A simple hypothesis could be that pesticides mixed together competed for the same receptor to favor the formation of a complex with reduced activity towards EREs. If these compounds are classified according to the level of Vtg secreted, we observed the following decreasing order: 17beta-estradiol (E(2))>o,p'-DDT>dieldrin>aldrin>DDT. Non-toxic levels of these compounds competed with E(2) for binding to the estrogen receptor. Heptachlor and mirex did not induce Vtg. Since the latter compounds failed to stimulate Vtg production, the possibility that they could interfere with the estrogenic response by inhibiting E(2) action was tested. In the presence of heptachlor, Vtg production triggered by E(2) significantly decreased. The EC50 value for inhibition of ER binding by heptachlor was cytotoxic for hepatocytes in culture, and this could in part explain the lack of Vtg response observed with this compound at the concentrations tested. Our results indicate that organochlorine pesticides can act as positive or negative modulators of estrogenic function in rainbow trout.

Animals↗
PubMedDate not supplied

The presence of environmental pollutants in the semen of farm animals (bull, ram, goat, and boar).

Organochlorine pesticides and polychlorinated biphenyls are widely used in agriculture and industry, respectively, and may affect male reproduction function. Although several pollutants have been detected in human semen, similar studies in farm animals have not appeared. In the present study, the semen of bulls, rams, goats, and boars was assayed for the organochlorine pesticides hexachlorobenzene (HCB), hexachlorocyclohexane (HCH, alpha-, beta-, and gamma-isomers), dieldrin, and heptachlor epoxide, for DDT-related chemicals (o,p'-DDE, p,p'-DDE, p,p'-DDD, p,p'-DDT), and for the PCBs congeners (PCB-52, -101, -138, -150, and -180). In all species of farm animals, the most frequently detected pollutants were p,p'-DDE (80-100% of samples), HCB (73.9-100%), and gamma-HCH (69.6-100%). Species differences in the concentrations of HCB, alpha-, beta-, and gamma-HCH, dieldrin, p,p'-DDE, p,p'-DDD, and PCBs were noted as well as differences in the concentrations of some isomers of HCH, DDT-related chemicals, and PCB congeners in the same species.

Animals↗
PubMed1999

Mechanisms of insecticide resistance in the aphid Nasonovia ribisnigri (Mosley) (Homoptera: Aphididae) from France.

Nasonovia ribisnigri, a main pest of salad crops, has developed resistance to various insecticides in southern France, including the carbamate pirimicarb and the cyclodiene endosulfan, two insecticides widely used to control this aphid. Here we have investigated the mechanisms of resistance to these two insecticides by studying cross-resistance, synergism, activity of detoxifying enzymes, and possible modifications of the target proteins. Resistance to pirimicarb was shown to be mainly due to a decreased sensitivity of the target acetylcholinesterase; this modification conferred also, resistance to propoxur but not to methomyl and the two tested organophosphates (acephate and paraoxon). Endosulfan resistance was associated with a moderate level of resistance to dieldrin, and resistance to both insecticides was due, in part, to increased detoxification by glutathione S-transferases (GST). The endosulfan resistant strain displayed the same amino acid at position 302 of the Rdl gene (GABA receptor) as susceptible aphids (e.g. Ala), indicating that the Ala to Ser (or to Gly) mutation observed among dieldrin resistant strains of other insect species was not present.

Animals↗
PubMed2002

Human blood and environmental media screening method for pesticides and polychlorinated biphenyl compounds using liquid extraction and gas chromatography-mass spectrometry analysis.

Screening assessment methods have been developed for semi- and non-volatile persistent organic pollutants (POPs) for human blood and solid environmental media. The specific methodology is developed for measuring the presence of "native" compounds, specifically, a variety of organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), and for polychlorinated biphenyls (PCBs). The method is demonstrated on anonymous Red Cross blood samples as well as two potential environmental sources, tracked in soil and dog hair. This work is based on previously developed methods for semi-volatile hydrocarbon exposure from fuels usage and similarly employs liquid solvent extraction, evaporative volume reduction. and subsequent specialized gas chromatography-mass spectrometry analysis (GC-MS). Standard curves, estimates of recovery efficiency, and specific GC-MS SIM quantification methods were developed for common pesticides including diazinon. aldrin, chlorpyrifos, malathion, dieldrin, DDT, permethrin, cyhalothrin, and cypermethrin, and for seven selected PCBs. Trace levels of certain PCBs and pesticides such as permethrin, dieldrin, malathion, lindane, diazinon, and chlorpyrifos were tentatively identified in anonymous blood samples as well as in two potential environmental sources. tracked in soil and dog hair. The method provides a simple screening procedure for various media and a variety of common organic pollutants without extensive sample preparation. It is meant to complement and augment data from more specific or complex methodology, to provide initial broad spectrum guidance for designing targeted experiments, and to provide confirmatory evidence for the usual metabolic biomarker measurements made to assess human exposure.

Environmental Monitoring↗
PubMed2001

Chlorinated cyclodiene pesticide residues in blue mussel, crab, and fish in the Gulf of Gdańsk, Baltic Sea.

Chlordane components (CHLs) and their metabolites (heptachlor, cis-heptachlor epoxide, U82, MC4, trans-chlordane, MC5, cis-chlordane, MC7, oxychlordane, MC6- and trans- and cis-nonachlor) and aldrin, dieldrin, endrin, isodrin, endosulfan 1, endosulfan 2, and mirex were quantified in the soft tissues of blue mussel, a whole crab, and whole fishes collected from the spatially different sites in the Gulf of Gdańsk. Six to twelve chlordane compounds and metabolites and dieldrin were detected in all organisms examined while aldrin, endrin, isodrin, endosulfans 1 and 2, and mirex were not found above the detection limit of the method. The lipid weight based concentrations in Baltic biota were relatively small and ranged from 12 to 150 and 7.6-77 ng/g, while between 0.16 and 6.8 and 0.10-6.6 ng/g in fresh tissue, respectively. The profile (%) of chlordane compounds was very similar between various fish species with trans-nonachlor (28 +/- 17), cis-chlordane (23 +/- 18), oxychlordane (13 +/- 7), and heptachlor epoxide (11 +/- 5) as major constituents and was totally different in crab with oxychlordane as the most dominating (>65%) compound. Blue mussel, lamprey, and three-spined stickleback exhibited a smallest ability to metabolize CHLs, and such fishes as cod, lesser sand-eel, sand-eel, pikeperch, perch, round goby, flounder, and herring showed a slightly better ability, while crab was able to effectively metabolize most of CHL compounds except trans-nonachlor. A value of the quotient of the trans-nonachlor to cis-chlordane concentrations (N/C quotient) was 1.0 in blue mussel, 3.1 in crab, and between 0.9 and 1.8 in fish. Both the small concentrations of CHLs in all organisms and the values of N/C quotients close to 1 imply on a long-range aerial transport through movement of the air masses from the remote regions of the northern hemisphere as a main source of this pesticide in the Gulf of Gdańsk. The interdependences between the CHL profiles for various fish species and between different sampling sites were examined using the principal component analysis (PCA) method. Applying the PCA model the first four significant components explained 90% (43% + 23% + 15% + 8%) of the total variance in the data matrix.

Animals↗
PubMed2004

Using passive air samplers to assess urban-rural trends for persistent organic pollutants. 1. Polychlorinated biphenyls and organochlorine pesticides.

Passive air samplers were used to investigate urban-rural differences of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) over an integrated time period. Samplers consisting of polyurethane foam (PUF) disks and semi-permeable membrane devices (SPMDs) were housed in protective chambers and deployed at six sites for a 4 month duration in the summer of 2000. The sampling transect originated in downtown Toronto and extended approximately 75 km northward into a rural region. Results for the two types of samplers agreed well with one another. Higher blank levels were encountered for the SPMDs, especially for the OCPs, whereas blanks were very low for the PUF disks. Passive sampler-derived air concentrations were consistent with previous measurements of PCBs and OCPs in the region. The largest urban-rural gradient was observed for PCBs (approximately 5-10 times). Chlordanes also showed an urban-rural gradient, possibly reflecting past usage of chlordane on residential lawns and emissions from treated house foundations. Other OCPs exhibited a rural-urban gradient (dieldrin, endosulfan 1, and DDT isomers), which was attributed either to off-gassing from previously treated agricultural soils (dieldrin and DDTs) or to continued usage in agriculture (endosulfan 1). The results of this study demonstrated the feasibility of using such devices to determine air concentrations of persistent organic pollutants (POPs) and to assess their spatial distribution for time-integrated samples. Data such as this is essential for: model validation and for process research and addressing international monitoring strategies on POPs.

Air Pollutants↗
PubMed2006

Preliminary assessment of imidazolium-based room-temperature ionic liquids for extraction of organic contaminants from soils.

Alternative solvents known as room-temperature ionic liquids (RTILs) were considered for extraction of organic soil contaminants. A hydrophobic RTIL, 1-butyl-3-methyl imidazolium hexafluorophosphate ([bmim]PF6), and a hydrophilic RTIL, 1-butyl-3-methyl imidazolium chloride ([bmim]Cl), were selected as representative imidazolium-based RTILs to assess the extraction of several organic contaminants (OCs) from two model soils. The two soils were montmorillonite (clay minerals, high surface area, and no organic matter) and glacial till (organic matter). The soils were spiked separately with DDT, dieldrin, hexachlorobenzene, and pentachlorophenol. With the exception of DDT, extractions of OCs from montmorillonite using [bmim]PF6 (79-92%) were nearly as effective as extractions with acetone and ethanol (85-100%). The extraction of OCs from glacial till with RTILs (15-61%) was less effective than extraction with organic solvents (59-100%). The [bmim]Cl was as efficient as [bmim]PF6 for extraction of OCs from glacial till, while [bmim]PF6 was more efficient than [bmim]Cl for extraction of OCs from montmorillonite. The two RTILs were most effective for the extraction of dieldrin (the heaviest OC) from both soils. The extraction results for glacial till showed dependence of OC extraction on the viscosity and melting point of RTILs.

Imidazoles↗
PubMed2006

Toward a global network for persistent organic pollutants in air: results from the GAPS study.

The Global Atmospheric Passive Sampling (GAPS) study aims to demonstrate the feasibility of using passive samplers to assess the spatial distribution of persistent organic pollutants on a worldwide basis. The GAPS network includes more than 40 sites on 7 continents, mainly in background locations, with some representation of urban and agricultural areas. Here we present concentrations of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) in polyurethane foam disk samplers, deployed from December 2004 to March 2005. Legacy OCPs such as alpha-HCH (hexachlorocyclohexane), Chlordanes (trans- and cis-Chlordane and trans-Nonachlor), Dieldrin, and dichlorodiphenyltrichloroethane isomers were detected at most sites with some high values that may be related to possible continued use and/or re-emissions related to historic use. Geometric mean (GM) air concentrations (pg/m3) were: 8.5 for sigmaHCH (sum of alpha- and gamma-isomers), 2.6 for sigmaChlordanes, 0.8 for Dieldrin, and 0.8 for p,p'-DDE. Current-use pesticides such as gamma-HCH (lindane) and especially Endosulfan I exhibited more variable and higher concentrations with GMs of 5 and 58, respectively. PCBs and PBDEs were elevated at urban/suburban sites consistent with their historical use pattern. GM concentrations (pg/m3) were 17 for PCBs and 4 for PBDEs. Sampling under GAPS will continue and will eventually allow seasonality effects and longer-term temporal and spatial trends to be evaluated.

Air Movements↗
PubMed2003

Organochlorine pesticide residues in leek (Allium porrum) crops grown on untreated soils from an agricultural environment.

Leek (Allium porrum) plants from organic farming were harvested at 15, 59, and 210 days after seed germination. Organochlorine pesticide (OCP) levels were quantified by GC-ECD in vegetative tissues (roots and aerial), bulk soil and rhizosphere. Leek plant bioaccumulate OCPs efficiently in their aerial and root tissues and alter the concentration of the soil where they are grown. OCPs distribution pattern of bulk soil was endosulfans > DDTs > dieldrin, while it was endosulfans > HCHs > DDTs in leek tissues. There were statistically significant declines in DDTs, chlordane, dieldrin, and heptachlor in the rhizosphere, indicating that recalcitrant residues of OCPs may be removed from contaminated soil using leek crops under normal growing conditions. The DDE/DDT and alpha-/gamma-HCH ratios of < 1 would indicate recent inputs of DDT and lindane in the environment. The occurrence of OCPs in this farm could be the result of atmospheric deposition and/or surface runoff of these pesticides.

Agriculture↗
PubMed2002

Organochlorines, p53 mutations in relation to breast cancer risk and survival. A Danish cohort-nested case-controls study.

Epidemiological studies integrating genetic susceptibility with biological measurements of organochlorine exposure may provide new clues regarding these substances influence on breast cancer etiology. Initial attempts pursuing this avenue has dealt with polymorphisms in the carcinoge metabolizing enzymes cytochrome P450 (CYP1A1). This study examined if mutations in the tumor suppressor gene p53 affected organochlorine exposure related breast cancer risk and survival. The material consisted of 162 breast cancer cases and 316 matched controls, who had participated, in the Copenhagen City Heart Study (CCHS) between 1976 and 1978. Cases diagnosed between study initiation and 1993 were identified by linkage to the Danish Cancer Registry. The case group served as a cohort in the survival analyses. Information on known and suspected breast cancer risk factors was obtained from CCHS, and the Danish Breast Cancer Cooperative Group provided information on tumor characteristics. Lipid adjusted serum concentrations of selected organochlorines were compared between cases and controls while stratifing by p53 mutation status. A non-significant increased risk of breast cancer was observed in the highest exposure level of dieldrin and polychlorinated biphenyls among women who developed a tumor with mutant p53 (odds ratio (OR) = 3.53, 95% confidence interval (CI) = 0.79-15.79 and OR = 3.00, 95% CI = 0.66-13.62). There was no clear difference in overall survival between breast cancer cases with 'wild-type' and mutant p53, although a significant dose-response relationship appeared for dieldrin exposure in tumors with 'wild-type' p53. These preliminary results suggest that p53 mutations may have a modifying effect on at least the breast cancer risk associated with exposures to organochlorines.

Adult↗
PubMed1997

Effects of [3H]-BIDN, a novel bicyclic dinitrile radioligand for GABA-gated chloride channels of insects and vertebrates.

1. The radiolabelled bicyclic dinitrile, [3H]-3,3-bis-trifluoromethyl-bicyclo[2.2.1]heptane-2,2-dicarbonitrile ([3H]-BIDN), exhibited, specific binding of high affinity to membranes of the southern corn rootworm (Diabrotica undecimpunctata howardi) and other insects. A variety of gamma-aminobutyric acid (GABA) receptor convulsants, including the insecticides heptachlor (IC50, 35 +/- 3 nM) and dieldrin (IC50, 93 +/- 7 nM), displaced [3H]-BIDN from rootworm membranes. When tested at 100 microM, 1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]oct ane(EBOB), 4-t-butyl-2,6,7-trioxa-1-phosphabicy-clo[2.2.2]octane-1-thio ne (TBPS), 1-phenyl-4-t-butyl-2,6,7-trioxabicyclo[2.2.2]octane (TBOB) and picrotoxin failed to displace 50% of [3H]-BIDN binding to rootworm membranes indicating that the bicyclic dinitrile radioligand probes a site distinct from those identified by other convulsant radioligands. 2. Dissociation studies showed that dieldrin, ketoendrin, toxaphene, heptachlor epoxide and alpha and beta endosulphan displace bound [3H]-BIDN from rootworm membranes by a competitive mechanism. 3. Rat brain membranes were also shown to possess a population of saturable, specific [3H]-BIDN binding sites, though of lower affinity than in rootworm and with a different pharmacological profile. Of the insecticidal GABAergic convulsants that displaced [3H]-BIDN from rootworm, cockroach (Periplaneta americana) and rat brain membranes, many were more effective in rootworm. 4. Functional GABA-gated chloride channels of rootworm nervous system and of cockroach nerve and muscle were blocked by BIDN, whereas cockroach neuronal GABA(B) receptors were unaffected. 5. Expression in Xenopus oocytes of either rat brain mRNA, or cDNA-derived RNA encoding a GABA receptor subunit (Rdl) that is expressed widely in the nervous system of Drosophila melanogaster resulted in functional, homo-oligomeric GABA receptors that were blocked by BIDN. Thus, BIDN probes a novel site on GABA-gated Cl- channels to which a number of insecticidally-active molecules bind.

Animals↗
PubMed2003

Pharmacological characterization of the homomeric and heteromeric UNC-49 GABA receptors in C. elegans.

(1) UNC-49B and UNC-49C are gamma-aminobutyric acid (GABA) receptor subunits encoded by the Caenorhabditis elegans unc-49 gene. UNC-49B forms a homomeric GABA receptor, or can co-assemble with UNC-49C to form a heteromeric receptor. The pharmacological properties of UNC-49B homomers and UNC-49B/C heteromers were investigated in Xenopus oocytes. (2) The UNC-49 subunits are most closely related to the bicuculline- and benzodiazepine-insensitive RDL GABA receptors of insects. Consistent with this classification, bicuculline (10 micro M) did not inhibit, nor did diazepam (10 micro M) enhance UNC-49B homomeric or UNC-49B/C heteromeric receptors. (3) The UNC-49C subunit strongly affects the pharmacology of UNC-49B/C heteromeric receptors. UNC-49B homomers were much more picrotoxin sensitive than UNC-49B/C heteromers (IC(50)=0.9+/-0.2 micro M and 166+/-42 micro M, respectively). Pentobarbitone enhancement was greater for UNC-49B homomers compared to UNC-49B/C heteromers. Propofol (50 micro M) slightly enhanced UNC-49B homomers but slightly inhibited UNC-49B/C heteromers. Penicillin G (10 mM) inhibited UNC-49B homomers less strongly than UNC-49B/C heteromers (30% compared to 53% inhibition, respectively). (4) Several aspects of UNC-49 pharmacology were unusual. Picrotoxin sensitivity strongly correlates with dieldrin sensitivity, yet UNC-49B homomers were highly dieldrin resistant. The enhancing neurosteroid pregnanolone (5beta-pregnan-3alpha-ol-20-one; 10 micro M) strongly inhibited both UNC-49 receptors. Alphaxalone (10 micro M), another enhancing neurosteroid, did not affect UNC-49B homomers, but slightly inhibited UNC-49B/C heteromers. (5) UNC-49 subunits and mammalian GABA(A) receptor alpha, beta, and gamma subunit classes all share roughly the same degree of sequence similarity. Thus, although they are most similar to other invertebrate GABA receptors, the UNC-49 receptors share significant structural and pharmacological overlap with mammalian GABA(A) receptors.

Amino Acid Sequence↗