In <i>Vitro</i> Modulation by Avermectin B<sub>1</sub>a of the GABA/Benzodiazepine Receptor Complex of Rat Cerebellum

Supavilai, Porntip; Karobath, Manfred

doi:10.1111/j.1471-4159.1981.tb01664.x

Cited by 36 publications

(14 citation statements)

References 15 publications

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“…In this study, tail contractions were absent but no gross morphological defects were observed among embryos exposed to abamectin insecticide from 5–25 hpf. This absence of movement is consistent with other studies showing abamectin neurotoxicity being linked to it agonizing GABA receptors that stimulates release of GABA neurotransmitter and produces paralytic responses 207–209 .…”

Section: Behavioral Testing In Zebrafishsupporting

confidence: 92%

Zebrafish as an in vivo model for sustainable chemical design

2016

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Heightened public awareness about the many thousands of chemicals in use and present as persistent contaminants in the environment has increased the demand for safer chemicals and more rigorous toxicity testing. There is a growing recognition that the use of traditional test models and empirical approaches is impractical for screening for toxicity the many thousands of chemicals in the environment and the hundreds of new chemistries introduced each year. These realities coupled with the green chemistry movement have prompted efforts to implement more predictive-based approaches to evaluate chemical toxicity early in product development. While used for many years in environmental toxicology and biomedicine, zebrafish use has accelerated more recently in genetic toxicology, high throughput screening (HTS), and behavioral testing. This review describes major advances in these testing methods that have positioned the zebrafish as a highly applicable model in chemical safety evaluations and sustainable chemistry efforts. Many toxic responses have been shown to be shared among fish and mammals owing to their generally well-conserved development, cellular networks, and organ systems. These shared responses have been observed for chemicals that impair endocrine functioning, development, and reproduction, as well as those that elicit cardiotoxicity and carcinogenicity, among other diseases. HTS technologies with zebrafish enable screening large chemical libraries for bioactivity that provide opportunities for testing early in product development. A compelling attribute of the zebrafish centers on being able to characterize toxicity mechanisms across multiple levels of biological organization from the genome to receptor interactions and cellular processes leading to phenotypic changes such as developmental malformations. Finally, there is a growing recognition of the links between human and wildlife health and the need for approaches that allow for assessment of real world multi-chemical exposures. The zebrafish is poised to be an important model in bridging these two conventionally separate areas of toxicology and characterizing the biological effects of chemical mixtures that could augment its role in sustainable chemistry.

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Section: Behavioral Testing In Zebrafishsupporting

confidence: 92%

Zebrafish as an in vivo model for sustainable chemical design

2016

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“…Like GABA, AVM protected BZ receptor binding sites from heat inactivation, whereas barbiturates and pyrazolopyridines were ineffective . AVM enhancement of BZ binding was additive with that of GABA agonists, and diminished by high concentrations of pyrazolopyridines and some GABA "partial" agonists (Supavilai and Karobath, 1981~;Williams and Risley, 1984).…”

Section: Avm Is a Glycosidic Macrocyclic Lactone Frommentioning

confidence: 93%

“…AVM enhancement (EC,, -30 nM) of BZ binding (both KD and B,,,) has been observed by numerous groups (Williams and Yarbrough, 1979;Paul et al, 1980;Supavilai and Karobath, 1981~;. AVM enhancement was reported in one study to be unaffected by bicuculline methiodide (10 pLIM) (Supavilai and Karobath, 1981~) but others found a partial block by higher concentrations of bicuculline (50-100 pn/r) but not strychnine or picrotoxin (100 pM) (Paul et al, 1980).…”

Section: Avm Is a Glycosidic Macrocyclic Lactone Frommentioning

confidence: 93%

“…The pyrazolopyridine and barbiturate enhancement of BZ binding were reported to be chloridedependent and inhibited by picrotoxin and related GABA chloride channel antagonists, as well as by bicuculline and related GABA receptor antagonists (Supavilai et al, 1981;Asano and Ogasawara, 1981;Leeb-Lundberg et al, 1980Skolnick et al, 1982;Ticku and Maksay, 1983). Further, these depressant compounds at similar concentrations inhibited the binding of [3H]a-dihydropicrotoxinin (Olsen, 1981) and [3sS]TBPS (Squires et al, 1983;Ticku and Maksay, 1983;King and Olsen, 1984;Supavilai and Karobath, 1984) to the convulsant receptor sites.…”

Section: Avm Is a Glycosidic Macrocyclic Lactone Frommentioning

confidence: 99%

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Avermectin B_la Modulation of γ‐Aminobutyric Acid/Benzodiazepine Receptor Binding in Mammalian Brain

Olsen

Snowman

1985

Journal of Neurochemistry

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The anthelminthic natural product avermectin B1a (AVM) modulates the binding of gamma-aminobutyric acid (GABA) and benzodiazepine (BZ) receptor ligands to membrane homogenates of mammalian brain. The potent (EC50 = 40 nM) enhancement by AVM of [3H]diazepam binding to rat or bovine brain membranes resembled that of barbiturates and pyrazolopyridines in being inhibited (partially) by the convulsants picrotoxin, bicuculline, and strychnine, and by the anticonvulsants phenobarbital and chlormethiazole. The maximal effect of AVM was not increased by pentobarbital or etazolate. However, AVM affected BZ receptor subpopulations or conformational states in a manner different from pentobarbital. Further, unlike pentobarbital and etazolate, AVM did not inhibit allosterically the binding of the BZ receptor inverse agonist [3H]beta-carboline-3-carboxylate methyl ester, nor did it inhibit, but rather enhanced, the binding of the cage convulsant [35S]t-butyl bicyclophosphorothionate to picrotoxin receptor sites. AVM at submicromolar concentrations had the opposite effect of pentobarbital and etazolate on GABA receptor binding, decreasing by half the high-affinity binding of [3H]GABA and related agonist ligands, and increasing by over twofold the binding of the antagonist [3H]bicuculline methochloride, an effect that was potentiated by picrotoxin. AVM also reversed the enhancement of GABA agonists and inhibition of GABA antagonist binding by barbiturates and pyrazolopyridines. These overall effects of AVM are unique and require the presence of another separate drug receptor site on the GABA/BZ receptor complex.

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“…Avermectin binds specifically to brain membranes, and enhances GABA binding (Wang & Pong, 1982). Supavilai & Karobath (1981) have also suggested that avermectin enhances benzodiazepine binding to a novel modulatory site on the GABA-benzodiazepine receptor/complex. Whether these effects are correlated with the slow agonist actions of this compound is not yet known.…”

Section: Halothane Ketamine and Diazepammentioning

confidence: 99%

Actions of anaesthetics and avermectin on GABA_A chloride channels in mammalian dorsal root ganglion neurones

Robertson

1989

British J Pharmacology

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1 The y-aminobutyric acid (GABA)-mimetic actions of some anaesthetics and the antehelminthic avermectin B1a were examined on freshly isolated mammalian dorsal root ganglion (DRG) neurones by use of suction electrodes and a single electrode voltage clamp.2 Pentobarbitone (60yM-3mM), chloralose (600yM-1mM), etomidate (10-100 pM), alphaxalone (10-60pM) and avermectin (10-60pM) directly activated chloride channels in GABA-sensitive DRG neurones. The agonist action was sensitive to block by bicuculline and picrotoxinin. 3 Steady-state current-voltage (I-V) curves for the anaesthetics were either linear, or rectified in the opposite direction to steady-state I-V curves obtained with GABA. Current relaxations in response to voltage jumps were also of the opposite direction. An extra surge of current ('bounce') was commonly observed on washout of some of these agonists. 4 Pentobarbitone was ineffective as an agonist at alkali pH (10.4 and 9.4), but was approximately twice as effective at acid (5.4) than at normal (7.4) pH values. 5 These results suggest that some anaesthetics and avermectin are capable of 'blocking' GABA channels in addition to activating them.

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In Vitro Modulation by Avermectin B₁a of the GABA/Benzodiazepine Receptor Complex of Rat Cerebellum

Cited by 36 publications

References 15 publications

Zebrafish as an in vivo model for sustainable chemical design

Zebrafish as an in vivo model for sustainable chemical design

Avermectin B_la Modulation of γ‐Aminobutyric Acid/Benzodiazepine Receptor Binding in Mammalian Brain

Actions of anaesthetics and avermectin on GABA_A chloride channels in mammalian dorsal root ganglion neurones

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In Vitro Modulation by Avermectin B1a of the GABA/Benzodiazepine Receptor Complex of Rat Cerebellum

Cited by 36 publications

References 15 publications

Zebrafish as an in vivo model for sustainable chemical design

Zebrafish as an in vivo model for sustainable chemical design

Avermectin Bla Modulation of γ‐Aminobutyric Acid/Benzodiazepine Receptor Binding in Mammalian Brain

Actions of anaesthetics and avermectin on GABAA chloride channels in mammalian dorsal root ganglion neurones

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In Vitro Modulation by Avermectin B₁a of the GABA/Benzodiazepine Receptor Complex of Rat Cerebellum

Avermectin B_la Modulation of γ‐Aminobutyric Acid/Benzodiazepine Receptor Binding in Mammalian Brain

Actions of anaesthetics and avermectin on GABA_A chloride channels in mammalian dorsal root ganglion neurones