Peptides and the human colon: an in vitro pharmacological study

Abstract

Longitudinal and circular strips of human colon isolated in vitro respond with dose-dependent contractions to angiotensin II, bradykinin, substance P, neurotensin, bombesin, histamine and carbachol and are inhibited by the vasoactive intestinal peptide. The octapeptide (26-33) of cholecystokinin contracts only the longitudinal muscle, while 5-hydroxytryptamine (5-HT) contracts the circular and inhibits the longitudinal muscle strip. Opioid peptides, somatostatin, secretin, motilin, glucagon, insulin and the C-terminal tetrapeptide of gastrin are inactive as stimulants or relaxants. The sensitivity of the human colon to des-Arg9-bradykinin, a specific stimulant of B1 receptors for kinins, increases progressively with the incubation time in vitro. The response of the colon to des-Arg9-bradykinin is blocked by [Leu9]-des-Arg10-kallidine (KD), a specific inhibitor of B1 receptors for kinins. The myotropic effect of neurotensin is not antagonized by [D-Trp11]-neurotensin, while that of angiotensin II is blocked by [Leu8]-angiotensin II. Substance P appears to exert its stimulant action through the activation of specific receptors as its effect is not influenced by a variety of inhibitors (atropine, propranolol, methysergide, diphenhydramine, [Leu8]-angiotensin II, [Leu9]-des-Arg10-KD and haloperidol) or by indomethacin and baclofen. The stimulant actions of bradykinin and angiotensin II appear to be due to the activation of specific receptors on the smooth muscle fibers, but indirect actions of the peptides on nervous cells cannot be excluded. Phentolamine and opioid peptides (Met-enkephalin, dynorphin) potentiate the actions of substance P, bradykinin, and angiotensin probably by interfering with the function of the intramural autonomic nervous system.