Evidence That the Action of Cholecystokinin Octapeptide on the Guinea Pig Ileum Longitudinal Muscle is Mediated in Part by Substance P Release from the Myenteric Plexus

Studies were made on the mode of action of cholecystokinin octapeptide (CCK8) on longitudinal muscle strips of guinea pig ileum in vitro. CCK8 produced dose-related contractions of innervated strips of ileum longitudinal muscle (EC50 3--4 x 10(-9) M), but was inactive on denervated strips. Tetrodotoxin, and reducing the bath temperature to 15 degree C, abolished the response of innervated strips to CCK8. These results indicate that the action of CCK8 on ileal longitudinal muscle is mediated by the myenteric plexus. Atropine abolished the responses to acetylcholine and to low doses of CCK8. However, the responses to CCK8 in doses above 10(-8) M were reduced by atropine but not abolished. Incubation of longitudinal muscle strips with high concentrations of substance P (1.5 x 10(-7) M) resulted in desensitization to this peptide; this treatment inhibited the responses to CCK8 alone, and abolished the atropine-resistant actions of CCK8. Desensitization to substance P had no effect on the responses to acetylcholine, histamine, serotonin and angiotensin II. The results indicate that CCK8 contracts the longitudinal muscle of guinea pig ileum by releasing acetylcholine and substance P from the myenteric plexus.