Pharmacological analysis of the mechanism of action for colonic contraction induced by neurotensin, substance P and methionine‐enkephalin

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Abstract
Infusion of neurotensin, substance P and methionine‐enkephalin induces colonic contraction in the cat. The present study was performed to investigate the effect of various pharmacological blocking agents on colonic contraction evoked by these peptides infused by the i.a. or i.v. route. The contractions caused by infusions of neurotensin were blocked by tetrodotoxin (1 μg kg‐1i.a.), hexamethionium (10 mg kg‐1i.v.), atropine(o.1 mg kg‐1i.v.) or somatostatin (100 pmol min‐1i.a.), but not by haloperidol, methysergide, mepyramine, cimetidine or naloxone. The contractile effect of substance P on the colon was abolished by the substance P receptor antagonist (D‐Arg1, D‐Pro2, D‐Trp7,9, Leu11)‐substance P (70 nmol min‐1i.a.). No other blockers used, such as tetrodotoxin, hexamethonium, atropine, mepyramine, cimetidine, methysergide, naloxone or somatostatin inhibited the response to substance P. Methionine‐enkephalin produced a colonic contraction that was completely blocked by naloxone (1 mg kg‐1i.a.). Both atropine (0.1 mg kg‐1i.v.) and somatostatin (100 pmol min‐1i.a.) reduced the contractile response. However, tetrodotoxin, hexamethonium, mepyramine, cimetidine and methysergide did not affect the response to methionine‐enkephalin. All adrenergic blockers tested, that is, guanethidine, propranolol and phentolamine, increased the contractile responses to the peptides. The results indicate that the colonic contraction induced by neurotensin is mediated via nervous cholinergic pathways. Substance P induces colonic contraction, probably by a direct effect on smooth muscle substance P receptors. Methionine‐enkephalin induces colonic contraction which could be blocked by naloxone. However, a cholinergic or peptidergic link may also be involved in the response to methionine‐enkephalin.