EVIDENCE FOR PHARMACOLOGICALLY DISTINCT GABA(B) RECEPTORS ASSOCIATED WITH CAMP PRODUCTION IN RAT-BRAIN

gamma-Aminobutyric acid-B (GABA(B)) receptors mediate a variety of cel lular functions, suggesting the possibility of pharmacologically and m olecularly distinct receptors. To explore this possibility a number of GABA(B) receptor agonists and antagonists were examined for their abi lity to influence cAMP production in rat brain cerebral cortical slice s. While the agonists did not differentiate between receptors associat ed with the augmentation of isoproterenol-induced cAMP production and those mediating inhibition of forskolin-stimulated second messenger ac cumulation, significant differences were noted between the potencies o f some antagonists to inhibit these GABA(B) receptor-mediated response s. The results suggest at least two pharmacologically distinct subclas ses of GABA(B) receptors regulate cAMP production in brain.