Effect of cholecystokinin-octapeptide on lower esophageal sphincter.

The effect of cholecystokinin-octapeptide (CCK-OP) on the lower esophageal sphincter (LES) was studied in 50 cats in vivo. CCK-OP caused a dose-dependent fall in LES pressures in all but 4 animals. Maximal sphincter relaxation was obtained with 200 to 400 ng of CCK-OP per kg of body weight. Atropine sulfate and/or hexamethonium, or adrenergic blocking agents (phentolamine or propranolol), in doses that completely inhibit the action of maximal doses of their respective agonists, failed to block the CCK-OP effect. Tetrodotoxin, however, in doses that denervates the LES, antagonized the CCK-OP-induced sphincter relaxation. In these tetrodotoxin-treated animals, CCK-OP produced LES contraction similar to that observed after pentagastrin. These results suggest that CCK-OP stimulates the postganglionic nonadrenergic, noncholinergic inhibitory neurons responsible for sphincter relaxation. CCK-OP also stimulates the circular muscle by direct action causing LES contraction. The latter becomes apparent when the innervation of the LES is abolished by tetrodoxtin.