Article date: 1990/6/21
PubMed ID: 2169426
Journal name: European journal of pharmacology (ISSN: 0014-2999)
GABA (gamma-aminobutyric acid) receptors of Achatina fulica neurones have been classified into two types associated with neuronal inhibition and one type with excitation. The pharmacological features of muscimol I and baclofen types associated with inhibition were investigated in this study. Activation of muscimol I type receptors on TAN (tonically autoactive neurone) by GABA, muscimol and trans-4-aminocrotonic acid (TACA) produced a transient outward current (Iout) with an increase in membrane conductance (g). Their relative potencies at GABA ED50 (approximately 10(-4) M) were: GABA: muscimol: TACA = 1:0.6:0.3. The relation between Iout and g increase (delta g) induced by various concentrations of these compounds was linear. The Hill coefficients for GABA were close to 1.0. The GABA effects were potentiated by pentobarbitone, antagonized competitively by pitrazepin and non-competitively by picrotoxin and diazepam, and unaffected by bicuculline. The reversal potentials of the effects of GABA, muscimol and TACA on TAN changed under various [Cl-]0 according to the Nernst equation for Ec1, but not under various [K+]0 and [Na+]0. Activation of baclofen type GABA receptors on RPeNLN (right pedal nerve large neurone) by GABA and (+/-)-baclofen produced a slow Iout with an increase in g. The two compounds were almost equipotent (ED50: approximately 3 x 10(-4) M). The relation between Iout and delta g produced by various concentrations was linear. The Hill coefficients for GABA were also close to 1.0. The reversal potentials of GABA and (+/-)-baclofen on RPeNLN changed under various [K+]0 according to the Nernst equation for EK, but not under various [Cl-]0 and [Na+]0. The two compounds hardly affected the voltage-gated and slowly inactivating calcium current. The Iout produced by GABA and (+/-)-baclofen was reduced by tetraethylammonium chloride, but was unaffected by 4-aminopyridine, bicuculline, pitrazepin and picrotoxin. In conclusion, the pharmacological features of muscimol I type GABA receptors are partly comparable to those of mammalian GABAA receptors, except for the influences of bicuculline and diazepam: the features of the baclofen type GABA receptor, which did not occur with muscimol I type receptors in the same neurone, were similar to those of GABAB.
Author List: Kim K H, Takeuchi H
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: Crotonates; Dibenzazepines; Receptors, GABA-A; Picrotoxin; 4-aminocrotonic acid; Muscimol; gamma-Aminobutyric Acid; pitrazepin; Baclofen; Pentobarbital; Diazepam; Bicuculline;
Mesh terms: Animals; Baclofen/pharmacology; Bicuculline/pharmacology; Crotonates/pharmacology; Diazepam/pharmacology; Dibenzazepines/pharmacology; Electrophysiology; In Vitro Techniques; Kinetics; Muscimol/pharmacology; Neurons/drug effects; Pentobarbital/pharmacology; Picrotoxin/pharmacology; Receptors, GABA-A/drug effects; Snails/metabolism; gamma-Aminobutyric Acid/pharmacology;