Abstract
The gamma-aminobutyric acid (GABA) receptor is the major inhibitory receptor in vertebrate and invertebrate brains. Activation of this GABA A receptor, which traverses the membrane, results in its opening of an anionic channel that is part of the receptor protein and permeation of Cl- along its concentration gradient. Thus, Cl influxes producing membrane hyperpolarization.6,11 This GABA A receptor is inhibited competitively by bicuculline and allosterically by picrotoxinin and t-butylbicyclophosphorothionate (TBPS), which bind to another site that is closely associated with the Cl- channel component of the receptor protein. The GABAA receptor is studied biochemically by the characteristics and specificity or its binding of [35S]TBPS and also by monitoring its function in vitro, i.e. 36C1 influx that is induced by binding of GABA to the receptor in membrane vesicles, is inhibited by competitive and noncompetitive inhibitors and is potentiated by certain modulators. GABA A receptors also have a site that binds benzodiazepines and another that binds depressant barbiturates.14 Benzodiasepines are mostly potentiators of GABA receptor function (e.g., diazepam) increasing the receptor’s affinity for GABA and facilitating the frequency of opening of its Cl- channel, but a few benzodiazepines are inhibitors of diazepam action. There are also benzodiazepine modulators of receptor function, acting as convulsants or proconvulsants and thus are called inverse agonists (e.g., ethyl β-carboline-3-carboxylate).
Keywords
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Abalis IM, Eldefrawi ME, Eldefrawi AT, 1985, High affinity stereospecific binding of cyclodiene insecticides and gamma-hexachlorocyclohexane to gamma-aminobutyric acid receptors of rat brain, Pestic Biochem Physiol., 24:95–102.
Blair LAC, Levitan ES, Marshall J, Dionne VE, Barnard EA, 1988, Single subunits of the GABAa receptor form ion channels with properties of the native receptor, Science, 242:577–579.
Casida JE, Lawrence LJ, 1985, Structure activity correlations for interactions of biocyclophosphorus esters and some polycholorocycloalkane and pyrethroid insecticides with the brain specific t-butylbicyclophos- phorothionate receptor, Environ Health Perspect., 61:123–132.
Cole RJ, Dorner JW, 1986, Role of fungal tremorgens in animal disease, In: “Mycotoxins and Phycotoxins,” Steyn PS, Vleggaar R, eds., Elsevier, Amsterdam.
Cole RJ, Kirksey JW, Moore JH, Blankenship BR, Diener VL, Davis ND, 1972, Tremorgenic toxin from Penicillium verruculosum, Appl Microbiol., 24:248–250.
Eldefrawi AT, Eldefrawi ME, 1987, Receptors for gamma-aminobutryic acid and voltage-dependent chlorida channels as targets for drugs and toxicants, FASEB J., 1:262–271.
Enna SJ, Karbon EW, 1987, Receptor regulation: evidence for a relationship between phospholipid metabolism and neurotransmitter mediated cAMP formation in brain, Trends Pharmacol. Sci., 8:21–24.
Gant DB, Cole RJ, Valdes J J, Eldefrawi ME, Eldefrawi AT, 1987, Action of tremorgenic mycotoxins on GABAa receptor, Life Sci.t 41:2207–2214.
Gant DB, Eldefrawi ME, Eldefrawi AT, 1987, Cyclodiene insecticides inhibit GABA receptor-regulated chloride transport, Toxicol Appl Pharamcol., 88:313–321.
Maksay G, Ticky MK, 1985, Dissociation of [35St-butylbicyclophosphoro- thionate binding differentiates convulsant and depressant drugs that modulate GABAergic transmission, J Neurochem., 44:480–486.
Olsen RW, 1982, Drug interactions at the GABA receptor-ionophore complex, Ann Rev Pharmacol Toxicol., 22:245–277.
Schof ield PR, Darlison MG, Fuj ita N, Burt DR, Stephenson FA, Rodriguez H, Rhee LM, Ramachandran J, Reale V, Glencorse TA, Seeburg PH, Barnard EA, 1987, Sequence and functional expression of the GABA receptor super- family, Nature, 328:221–227.
Ticku MK, Lowrimore P, Lehoullier P, 1986, Ethanol enhances GABA-induced 36C1 influx in primary spinal cord cultured neurons, Brain Res Bull., 17:123–126.
Trifiletti RR, Snowman AM, Snyder SH, 1985, Barbiurtrate recognition site on the GABA/benzodiazepine receptor complex is distinct from the picro- toxinin/TBPS recognition site, Eur J Pharmacol., 106:441–447.
Yao Y, Peter AB, Baur R, Sigel E, The tremorigen aflatrem is a positive aliosteric modulator of the gamma-aminobutyric acid receptor channel expressed in Xenopus oocytes, Mol Pharmacol., 35:319–324.
Ziskind L, Dennis MJ, 1978, Depolarising effect of curare on embryonic rat muscles, Nature, 276:622–623.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Plenum Press, New York
About this chapter
Cite this chapter
Eldefrawi, M.E., Gant, D.B., Eldefrawi, A.T. (1990). The GABA Receptor and the Action of Tremorgenic Mycotoxins. In: Pohland, A.E., et al. Microbial Toxins in Foods and Feeds. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0663-4_27
Download citation
DOI: https://doi.org/10.1007/978-1-4613-0663-4_27
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-7916-7
Online ISBN: 978-1-4613-0663-4
eBook Packages: Springer Book Archive