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 studied rabbit tracheal smooth muscle under isometric conditions in vitro. SRIF did not change the contractile responses to electrical field stimulation and acetylcholine, but it inhibited the relaxant responses to isoproterenol in a concentration-dependent manner, an effect that was reversed by treatment of tissues with pertussis toxin (PTX). In contrast, the forskolin- and verapamil-induced relaxations were not altered by SRIF. SRIF also attenuated the increase in intracellular cyclic AMP levels in response to isoproterenol. These results suggest that SRIF may decrease beta-adrenoceptor-mediated muscle relaxation by acting at the site proximal to cyclic AMP synthesis, especially at PTX-sensitive GTP-binding regulatory protein, Gi, coupled to adenylate cyclase.