EFFECT OF SOMATOSTATIN ON CONTRACTILE AND RELAXANT RESPONSES OF TRACHEAL SMOOTH-MUSCLE IN RABBITS

To determine the effect of somatostatin (SRIF) on airway smooth muscle contractile and relaxant responses and its mechanism of action, we st udied rabbit tracheal smooth muscle under isometric conditions in vitr o. SRIF did not change the contractile responses to electrical field s timulation and acetylcholine, but it inhibited the relaxant responses to isoproterenol in a concentration-dependent manner, an effect that w as reversed by treatment of tissues with pertussis toxin (PTX). In con trast, the forskolin- and verapamil-induced relaxations were not alter ed by SRIF. SRIF also attenuated the increase in intracellular cyclic AMP levels in response to isoproterenol. These results suggest that SR IF may decrease beta-adrenoceptor-mediated muscle relaxation by acting at the site proximal to cyclic AMP synthesis, especially at PTX-sensi tive GTP-binding regulatory protein, G(i), coupled to adenylate cyclas e.