Inactivation of GABA receptors by phenoxybenzamine: effects on GABA-stimulated benzodiazepine binding in the central nervous system.
Treatment of particulate fractions of rat forebrain with phenoxybenzamine produced dose related inhibition of specific muscimol binding. Scatchard analysis revealed a significant reduction of binding sites but no change in affinity constant. The inhibition was not reversed by washing or incubation at 37 degrees C suggesting that phenoxybenzamine alkylates GABA receptors, i.e. acts as a non-competitive, non-equilibrium inhibitor. Phenoxybenzamine inhibited the GABA-induced increase in specific diazepam binding but had little direct effect on diazepam binding. Preincubation of synaptic membranes with GABA or muscimol, but not diazepam, protected the muscimol binding site from inactivation by phenoxybenzamine.
D000818:Animals; D001921:Brain / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000378:metabolism; D010643:Phenoxybenzamine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A; D013268:Stimulation, Chemical; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D010643:Phenoxybenzamine; D009118:Muscimol; D005680:gamma-Aminobutyric Acid