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 gui nea pig were used to determine whether neurotensin can inhibit the con tractile response produced by 10(-6) M carbachol by exerting a direct action on muscle cells. In addition, the inhibitory effect of 2',5'-di deoxyadenosine, an inhibitor of adenylate cyclase, and methylene blue, an inhibitor of guanylate cyclase, on the neurotensin-induced relaxat ion of gastric smooth muscle cells were examined. Neurotensin inhibite d the contractile response produced by carbachol in a dose-dependent m anner, 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 prod uced by neurotensin. These results strongly suggest that the action of neurotensin is mediated by cyclic GMP.