Antagonism of 5-hydroxytryptamine1A (5-HT1A) receptor-mediated modulation of adenylate cyclase activity by pindolol and propranolol isomers

The interactions of the stereoisomers of pindolol and propranolol with 5-hydroxytryptamine1A (5-HT1A) binding sites and adenylate cyclase activity were examined in rat hippocampus. (-)Pindolol and (-)propranolol displayed high affinity for 5-HT1A binding sites, and their affinities were not affected significantly by the addition of 10(-4) M GTP to the radioligand assay. The selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) decreased forskolin-stimulated adenylate cyclase activity. The (-)isomers of pindolol and propranolol did not affect basal or forskolin-stimulated activity but, at a concentration of 10(-5) M, they reversed the 8-OH-DPAT inhibition of the forskolin-stimulated cyclase activity. The (+)isomers were less potent in producing this effect. These data suggest that (-)pindolol and (-)propranolol are potent antagonists at 5-HT1A receptors in rat hippocampus.