SENSITIVITY OF HISTAMINE H-3 RECEPTOR AGONIST-STIMULATED [S-35] GTP-GAMMA[S] BINDING TO PERTUSSIS TOXIN

The effect of histamine H-3 receptor-selective ligands on [S-35]guanos ine 5'-o-(gamma-thio)triphosphate ([S-35]GTP gamma[S]) binding has bee n examined in rat cerebral cortical membranes. R(alpha)-Methylhistamin e and N-alpha-methylhistamine produced a concentration-dependent stimu lation of [S-35]GTP gamma[S] binding which was attenuated in the prese nce of the selective histamine H-3 receptor antagonist thioperamide. I n addition, treatment of brain membranes with pertussis toxin abolishe d the histamine H-3 receptor agonist stimulated binding of [S-35]GTP g amma[S]. These results provide the first evidence that histamine H-3 r eceptors couple directly to a G(i)/G(o) protein in mammalian brain.