Abstract
The transmitter-activated ion channels are known to be important target sites of a variety of therapeutic and toxic agents. The GABA-activated chloride channel has been shown to be modulated by general anesthetics, alcohols, and the pyrethroid, cyclodiene and lindane insecticides. The general anesthetics halothane, enflurane and isoflurane greatly augmented the GABA-activated current before desensitization took place, and suppressed it after desensitization at clinically relevant concentrations equivalent to 1-2 minimum alveolar concentrations. The stimulating effect appears to be a mechanism of general anesthesia. It seems that general anesthetics have a specific affinity for the GABA receptor-channel complex. Ethanol also augmented the GABA-activated peak chloride current with little or no effect on the desensitized sustained current. Longer chain alcohols n-butanol, n-hexanol, n-octanol, and n-decanol also exerted the same type of effect, with the potency and efficacy increasing with lengthening of the carbon chain.
The GABA receptor-channel complex has also been shown to be an important target site of certain insecticides. The type II pyrethroids deltamethrin and fenvalerate augmented the GABA-activated peak Chloride current when applied concurrently with GABA, but the effect was diminished as the pyrethroids were applied for long periods of time prior to GABA application. The latter effect might explaln the controversy In the literature regarding the pyrethroid action on the GABA system. The type I pyrethroid allethrin suppressed the GABA-activated peak chloride current when co-applied with GABA. Both types of pyrethroids suppressed the N-methyl-d-aspartate-induced current. Lindane and the cyclodienes dieldrin, endrin, heptachlor-epoxide, and isobenzan suppressed the GABA-activated chloride current. These effects can account for the convulsant action of lindane and the cyclodienes.
This is a preview of subscription content, log in via an institution to check access.
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
Akaike, N., Inoue, M., and Krishtal, O. A., 1986, ‘Concentration-clamp’ study of γ-aminobutyric-acid-induced chloride current. Kinetics in frog sensory neurones, J. Physiol. (London), 379:171–185.
Akaike, N., Yakushiji, T., Tokutomi, N., and Carpenter, D. O., 1987, Multiple mechanisms of antagonism of γ-aminobutyric acid (GABA) responses, Cell. Mol. Neurobiol., 7:97–103.
Bloomquist, J. R., and Soderlund, D. M., 1985, Neurotoxic insecticides inhibit GABA-dependent chloride uptake by mouse brain vesicles, Biochem. Biophys. Res. Comm., 133:37–43.
Bormann, J., Hamill, O. P., and Sakmann, B., 1987, Mechanism of anion permeation through channels gated by glycine and γ-aminobutyric acid in mouse cultured spinal neurones, J. Physiol (London)., 385:243–286.
Celentano, J. J., Gibbs, T. T., and Farb, D. H., 1988, Ethanol potentiates GABA-and glycine-induced chloride currents in chick spinal cord neurons, Brain Res., 455:377–380.
Chalmers, A. E., Miller, T. A., and Olsen, R. W., 1985, A pharmacological investigation of invertebrate GABA receptors, in: “Neurotox ’85. Neuropharmacology and Pesticide Action,” Univ. Bath, Abstr. pp. 41–42.
Crofton, K. M., Reiter, L. W., and Mailman, R. B., 1987, Pyrethroid insecticides and radioligand displacement from the GABA receptor chloride ionophore complex, Toxicol. Letters, 35:183–190.
Franks, N. P., and Lieb, W. R., 1987, What is the molecular nature of general anaesthetic target sites? Trends in Pharmacol. Sci., 8:169–174.
Frey, J., and Narahashi, T., 1990, Pyrethroid insecticides block calcium and NMDA-activated currents in cultured mammalian neurons, Biophys. J., in press.
Frey, J., Dichter, M., and Narahashi, T., 1989, Effects of lindane and fenvalerate on GABA-activated chloride currents in cultured hippocampal neurons, The Toxicologist, 9:149.
Gammon, D. W., and Sander, G., 1985, Two mechanisms of pyrethroid action: Electrophysiological and pharmacological evidence, NeuroToxicology 6(2):63–86.
Ghiasuddin, S. M., and Matsumura, F., 1982, Inhibition of gamma-aminobutyric acid (GABA)-induced chloride uptake by gamma-BHC and heptachlor epoxide, Comp. Biochem. Physiol., 73C:141–144.
Hamill, O. P., Marty, A., Neher, E., Sakmann, B., and Sigworth, F. J., 1981, Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches, Pflugers Arch., 391:85–100.
Haydon, D. A., and Urban, B. W., 1983, The effects of some inhalation anaesthetics on the sodium current of the squid giant axon, J. Physiol. (London), 341:429–439.
Haydon, D. A., and Urban, B. W., 1986, The actions of some general anaesthetics on the potassium current of the squid giant axon, J. Physiol. (London), 373:311–327.
Janoff, A. S., and Miller, K. W., 1982, A critical assessment of the lipid theories of general anaesthetic action, in: “Biological Membranes,” Vol. 4, D. Chapman, ed., Academic Press, London, pp. 417–476.
Lawrence, L. J., and Casida, J. E., 1983, Stereospecific action of pyrethroid insecticides on the γ-aminobutyric acid receptor-ionophore complex, Science, 221:1399–1401.
Lawrence, L. J., Gee, K. W., and Yamamura, H. I., 1985, Interactions of pyrethroid insecticides with chloride ionophore-associated binding sites, NeuroToxicology 6(2):87–98.
Lechleiter, J., and Gruener, R., 1984, Halothane shortens acetylcholine receptor channel kinetics without affecting conductance, Proc. Natl. Acad. Sci. USA, 81:2929–2933.
Lummis, S. C. R., Chow, S. C, Holan, G., and Johnston, G. A. R., 1987, γ-Aminobutyric acid receptor ionophore complexes: Differential effects of deltamethrin, dichlorodiphenyltrichloroethane, and some novel insecticides in a rat brain membrane preparation, J. Neurochem., 48:689–694.
Mancillas, J. R., Siggins, G. R., and Bloom, F. E., 1986, Systemic ethanol: Selective enhancement of responses to acetylcholine and somatostatin in hippocampus, Science, 231:161–163.
Matsumura, F., and Ghiasuddin, S. M., 1983, Evidence for similarities between cyclodiene type insecticides and picrotoxinin in their action mechanisms, J. Environ. Sci. Health, B18:1–14.
Matsumura, F., and Tanaka, K., 1984, Molecular basis of neuroexcitatory actions of cyclodiene-type insecticides, in: “Cellular and Molecular Neurotoxicology,” T. Narahashi, ed., Raven Press, New York, pp. 225–240.
Mehta, A. K., and Ticku, M. K., 1988, Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves γ-aminobutyric acidA-gated chloride channels, J. Pharmacol. Exp. Ther., 246:558–564.
Miller, K. W., Firestone, L. L., and Forman, S. A., 1987, General anesthetic and specific effects of ethanol on acetylcholine receptors. New York Acad. Sci., 492:71–87.
Nakahiro, M., Yeh, J. Z., Brunner, E., and Narahashi, T., 1989, General anesthetics modulate GABA receptor channel complex in rat dorsal root ganglion neurons, FASEB J., 3:1850–1854.
Nakahiro, M., Arakawa, O., and Narahashi, T., 1990, Ethanol and longer chain alcohols enhance GABA-activated Cl-current in rat dorsal root ganglion neurons, FASEB J., in press.
Narahashi, T., 1971, Effects of insecticides on excitable tissues, in: “Advances in Insect Physiology,” Vol. 8, J. W. L. Beament, J. E. Treherne and V. B. Wigglesworth, eds., Academic Press, London and New York, pp. 1–93.
Narahashi, T., 1976, Effects of insecticides on nervous conduction and synaptic transmisssion, in: “Insecticide Biochemistry and Physiology,” C. F. Wilkinson, ed., Plenum Press, New York, pp. 327–352.
Narahashi, T., 1985, Nerve membrane ionic channels as the primary target of pyrethroids, NeuroToxicology, 6(2):3–22.
Narahashi, T., 1987, Neuronal target sites of insecticides, in: “Sites of Action for Neurotoxic Pesticides,” R. M. Hollingworth and M. B. Green, eds., American Chemical Society Symposium Series, No. 356, ACS, Washington, DC, pp. 226–250.
Narahashi, T., 1988, Molecular and cellular approaches to neurotoxicology: Past, present and future, in: “Neurotox ’88: Molecular Basis of Drug and Pesticide Action,” G. G. Lunt, ed., Elsevier, Amsterdam, pp. 269–288.
Narahashi, T., 1990, The role of ion channels in insecticide action, in: “Insecticide Action: From Molecule to Organism,” T. Narahashi and J. E. Chambers, eds., Plenum Press, New York, in press.
Narahashi, T., and Frey, J. M., 1989, Lindane and cyclodiene insecticides block GABA-activated chloride current in cultured rat hippocampal neurons, Abstr. Soc. Neurosci., 15:1151.
Nestoros, J. N., 1980, Ethanol specifically potentiates GABA-mediated neurotransmission in feline cerebral cortex, Science. 209:708–710.
Nishio, M., and Narahashi, T., 1988, Ethanol enhances a component of GABA-gated Cl channel current in rat dorsal root ganglion neurons, Soc. Neurosci. Abstr., 14:642.
Ogata, N., Vogel, S. M., and Narahashi, T., 1988, Lindane but not deltamethrin blocks a component of GABA-activated chloride channels, FASEB J., 2:2895–2900.
Roth, S. H., 1979, Physical mechanisms of anesthesia, Ann. Rev. Pharmacol. Toxicol., 19:159–178.
Ruigt, G. S. F., 1984, Pyrethroids, in: “Comprehensive Insect Physiology, Biochemistry and Pharmacology,” Vol. 12, Chapter 7, G. A. Kerkut and L. I. Gilbert, eds., Pergamon Press, Oxford, pp. 183–263.
Seeman, P., 1972, The membrane actions of anesthetics and tranquilizers, Pharmacol. Rev., 24:583–655.
Siggins, G. R., Pittman, Q. J., and French, E. D., 1987, Effects of ethanol on CA1 and CA3 pyramidal cells in the hippocampal slice preparation: An intracellular study, Brain Res., 414:22–34.
Suzdak, P. D., Schwartz, R. D., Skolnick, P., and Paul, S. M., 1986, Ethanol stimulates γ-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes, Proc. Natl. Acad. Sci. USA. 83:4071–4075.
Ticku, M. K., Lowrimore, P., and Lehoullier, P., 1986, Ethanol enhances GABA-induced 36Cl-influx in primary spinal cord cultured neurons, Brain Res. Bull., 17:123–126.
Woolley, D. W., 1981, The neurotoxicity of DDT and possible mechanisms of action, in: “Mechanisms of Neurotoxic Substances,” K. N. Prasal and A. Vernadakis, eds., Raven Press, New York, pp. 95–141.
Wouters, W., and van den Bercken, J., 1978, Action of pyrethroids, Gen. Pharmacol., 9:387–398.
Yamasaki, T., and Ishii (Narahashi), T., 1957, Studies on the mechanism of action of insecticides. X. Nervous activity as a factor of development of γ-BHC symptoms in the cockroach, Botyu-Kagaku (Scientific Insect Control), 19:106–112. English translation, Japanese Contributions to the Study of the Insecticide-Resistance Problem. Published by the Kyoto University for the W.H.O., pp. 176–183.
Yamasaki, T., and Narahashi, T., 1958, Nervous activity as a factor of development of dieldrin symptoms in the cockroach. Studies on the mechanism of action of insecticides, XVI, Botyu-Kagaku (Scientific Insect Control), 23:47–54.
Yasui, S., Ishizuka, S., and Akaike, N., 1985, GABA activates different types of chloride-conducting receptor-ionophore complexes in a dose-dependent manner, Brain Res., 344:176–180.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Plenum Press, New York
About this chapter
Cite this chapter
Narahashi, T. (1991). Transmitter-Activated Ion Channels as the Target of Chemical Agents. In: Kito, S., Segawa, T., Olsen, R.W. (eds) Neuroreceptor Mechanisms in Brain. Advances in Experimental Medicine and Biology, vol 287. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5907-4_6
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5907-4_6
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5909-8
Online ISBN: 978-1-4684-5907-4
eBook Packages: Springer Book Archive