Bicuculline-insensitive GABA binding to catfish neuronal membranes

GABA receptor binding to mammalian neuronal membranes has been classified into at least 2 subtypes-GABA(A) and GABA(B) binding sites. In catfish brain GABA(A) receptor sites have previously been demonstrated. Evidence is now presented that under appropriate conditions which rule out GABA(A) receptor binding, [(3)H]GABA binds to membranes prepared from catfish brain. This binding is bicuculline-insensitive but differs enough from mammalian GABA(B) binding to cast some doubt on the idea that GABA(B) receptors exist in catfish brain. Specific binding was detected that was saturable and exhibited a dissociation constant of 4?M. (+/-)Baclofen, a potent inhibitor in rat brain, was a weak inhibitor, producing a maximum of 43% inhibition. This inhibitory effect could be enhanced, however, in the presence of 320 ?M isoguvacine. [(3)H]GABA binding was unaffected by bicuculline. Thus bicuculline-insensitive GABA binding sites exist in catfish brain but they differ in a number of ways from the GABA(B) receptor site found in mammals. Furthermore, a third [(3)H]GABA binding site appears to exist that is both baclofen- and bicuculline-insensitive, yet is inhibited by high concentrations of isoguvacine, a known GABA(A) agonist.