DIRECT INHIBITORY EFFECT OF NEUROTENSIN ON ISOLATED GASTRIC SMOOTH-MUSCLE CELLS OF GUINEA-PIG VIA THE CYCLIC-GMP SYSTEM

Smooth muscle cells isolated from the gastric muscle layers of the guinea pig were used to determine whether neurotensin can inhibit the contractile response produced by 10(-6) M carbachol by exerting a direct action on muscle cells. In addition, the inhibitory effect of 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, and methylene blue, an inhibitor of guanylate cyclase, on the neurotensin-induced relaxation of gastric smooth muscle cells were examined. Neurotensin inhibited the contractile response produced by carbachol in a dose-dependent manner, with an IC50 value of 5 nM. 2',5'-Dideoxyadenosine did not have any significant effect on the neurotensin-induced relaxation. On the other hand, methylene blue significantly inhibited the relaxation produced by neurotensin. These results strongly suggest that the action of neurotensin is mediated by cyclic GMP.