A re-examination of the GABA-inhibitory action of bicuculline on lobster muscle. 1981

T G Smart, and A Constanti

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.

UI MeSH Term Description Entries
D008121 Nephropidae Family of large marine CRUSTACEA, in the order DECAPODA. These are called clawed lobsters because they bear pincers on the first three pairs of legs. The American lobster and Cape lobster in the genus Homarus are commonly used for food. Clawed Lobsters,Homaridae,Homarus,Lobsters, Clawed,Clawed Lobster,Lobster, Clawed
D008566 Membranes Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures. Membrane Tissue,Membrane,Membrane Tissues,Tissue, Membrane,Tissues, Membrane
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001640 Bicuculline An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors. 6-(5,6,7,8-Tetrahydro-6-methyl-1,3-dioxolo(4,5-g)isoquinolin-5-yl)furo(3,4-e)1,3-benzodioxol-8(6H)one
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding
D018756 GABA Antagonists Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS. gamma-Aminobutyric Acid Antagonists,GABA Antagonist,GABA Receptor Antagonists,Acid Antagonists, gamma-Aminobutyric,Antagonist, GABA,Antagonists, GABA,Antagonists, GABA Receptor,Antagonists, gamma-Aminobutyric Acid,Receptor Antagonists, GABA,gamma Aminobutyric Acid Antagonists
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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