The inhibitory effects of nicotinic antagonists on currents elicited by GABA in rat hippocampal neurons.
The nicotinic antagonists d-tubocurarine and trimethaphan camsylate competitively inhibit GABA-induced currents. Hexamethonium, mecamylamine and dihydro-beta-erythroidine, other nicotinic antagonists, do not affect GABA-elicited currents. The trimethaphan effect is completely reversed by a putative convulsant receptor antagonist, alpha-isopropyl-alpha-methyl-gamma-butyrolactone, which implies that the trimethaphan binding site may be closely associated with the convulsant site. However, nicotine was ineffective in competing for either the d-tubocurarine or trimethaphan effect at the GABAA receptor. From these observations, we propose that the nicotinic and GABAA receptor ionophore complexes share similar configurational patterns that accommodate some of the same molecules. Possible mechanisms for the trimethaphan and d-tubocurarine blockades are discussed.
Wotring
V E
VE
Department of Pharmacological and Physiological Science, Saint Louis University Health Sciences Center, MO 63110-0250, USA.
Yoon
K W
KW
D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D008968:Molecular Conformation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D005680:gamma-Aminobutyric Acid