PERTUSSIS-TOXIN-SENSITIVE AIRWAY BETA-ADRENERGIC DYSFUNCTION BY SOMATOSTATIN

To elucidate the effect of somatostatin and its mechanism of action on airway B-adrenergic function, we studied canine bronchial smooth musc le under isometric conditions in vitro. Somatostatin (10(-6) M) inhibi ted the salbutamol-induced relaxation, so that the salbutamol concentr ation-response curves were displaced to higher concentrations (P<0.01) . This inhibition was dose dependent, the concentration of somatostati n required to produce a half-maximal effect being 1O(-8) M. The relaxa nt responses to forskolin were likewise inhibited by somatostatin, but those to dibutyryl 3',5'-adenosine cyclic monophosphate (DB-cAMP), ve rapamil and nitroprusside were not. Somatostatin inhibited the salbuta mol-induced accumulation of intracellular cAMP. These effects were abo lished by the somatostatin antagonist cycle [7-aminoheplanoyl-Phe-D-Tr p-Lys-Thr (Bz)l or pertussis toxin. These observations suggest that so matostatin down-regulates beta-adrenergic Function of airway smooth mu scle through activation of an inhibitory guanine nucleolide (GTP)-bind ing regulatory protein, G(i), coupled to adenylate cyclase.