Dual action of cholecystokinin-octapeptide on the guinea pig antrum

We examined the mechanism of action of cholecystokinin-octapeptide (CCK-OP) on longitudinal strips of the lesser and greater curvatures of the guinea pig antrum. In the strips of the lesser curvature, CCK-OP produced a concentration-dependent tonic contraction, which was significantly reduced by atropine, but not by tetrodotoxin. In contrast, CCK-OP caused a relaxation of the preparation of the greater curvature in a concentration-dependent manner. The relaxation induced by the peptide was enhanced by atropine, whereas it was blocked by tetrodotoxin. Propranolol, phentolamine, desensitization to adenosine-5'-triphosphate, and desensitization to vasoactive intestinal polypeptide had no effect on CCK-OP-induced relaxation. Cholecystokinin-octapeptide evoked the release of acetylcholine from strips of both sides, and it was not blocked by tetrodotoxin. These findings indicate that the mechanism of action of CCK-OP on the lesser curvature differs from that on the greater curvature. The peptide seems to act directly on smooth muscle cells and to stimulate cholinergic neural activity by sodium channel-independent mechanisms. Additionally, nonadrenergic inhibitory neurons appear to be activated by CCK-OP in the greater curvature.