BICUCULLINE-INSENSITIVE AND BACLOFEN-INSENSITIVE GAMMA-AMINOBUTYRIC-ACID BINDING TO RAT CEREBELLAR MEMBRANES

Up to 60% of gamma-[H-3]aminobutyric acid ([H-3]GABA) bound specifically to rat cerebellar membranes in the absence of Ca2+ was insensitive to the GABA(A) antagonist bicuculline and to the GABA(B) agonist baclofen. This indicates that a significant component of specifically bound [H-3]GABA is associated with non-GABA(A), non-GABA(B) binding sites. The presence of this binding component appeared seasonal, peaking in the month of September (early spring) each year over a 4-year period. The calcium independence and bicuculline and baclofen insensitivity of the binding indicate that this binding is not to the classical GABA(A) and GABA(B) binding sites. High concentrations of muscimol and isoguvacine inhibited non-GABA(A), non-GABA(B) binding. Scatchard analysis of the non-GABA(A), non-GABA(B) binding sites indicated two kinetic components: K(D1) = 42 nM and K(D2) = 9.2-mu-M; B(max1) = 1.6 pmol/mg of protein and B(max2) = 28 pmol/mg of protein.