γ‐Aminobutyric Acid_B Receptor Activation Modifies Agonist Binding to β‐Adrenergic Receptors in Rat Brain Cerebral Cortex

The interaction of isoproterenol with β‐adrenergic receptor (βAR) binding sites was measured in membranes prepared from rat brain cerebral cortical slices previously incubated in the presence or absence of γ‐aminobutyric acid (GABA) receptor agonists. Both GABA and baclofen, but not isoguvacine, altered βAR agonist binding by increasing the affinity of both the low‐ and high‐affinity binding sites and by increasing the proportion of low‐affinity receptors. The response to baclofen was stereoselective, and the effect of GABA was not inhibited by bicuculline. The results suggest that GABA_B, but not GABA_A, receptor activation modifies the coupling between βAR and stimulatory guanine nucleotide‐binding protein, which may in part explain the ability of baclofen to augment isoproterenol‐stim‐ulated cyclic AMP accumulation in brain slices.