A re-examination of the GABA-inhibitory action of bicuculline on lobster muscle.
The GABA-inhibitory action of bicuculline on lobster muscle was critically re-examined. Bicuculline (20-100 micrometers) depressed the GABA-evoked conductance increase in a reversible manner, the double reciprocal transformation of the GABA dose/conductance curves remaining linear. If bicuculline was assumed to be a pure non-competitive antagonist, then the observed depression of the GABA curves at high GABA concentrations was underestimated. Also, the action of bicuculline was not in accordance with a dualistic antagonism (competitive and pure non-competitive type). Regarding bicuculline as a "mixed" non-competitive antagonist however, gave a better overall fit to the experimental data. Combinations of bicuculline and picrotoxinin also depressed the GABA response in a manner expected from the combination of two "mixed" non-competitive antagonists. It was concluded that bicuculline (like picrotoxinin and picrotoxin) behaves as a "mixed" non-competitive rather than a pure non-competitive antagonist of GABA on lobster muscle. However bicuculline methochloride proved inactive on the lobster. Moreover, bicuculline itself became less effective in a more acidic solution (pH 5.6, where more of the protonated form would exist). An intracellular or intramembrane site of action of this antagonist was therefore postulated.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D018756:GABA Antagonists; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008566:Membranes / Q000502:physiology; D009132:Muscles / Q000187:drug effects*; D008121:Nephropidae / Q000502:physiology*
D018756:GABA Antagonists; D001640:Bicuculline