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.
Oksenberg
D
D
Department of Neurology, Stanford University, CA 94305.
Peroutka
S J
SJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D066298:In Vitro Techniques; D010869:Pindolol / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D005576:Colforsin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006160:Guanosine Triphosphate; D011433:Propranolol; D010869:Pindolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases