Effects of substance P, cholecystokinin octapeptide, bombesin, and neurotensin on the peristaltic reflex of the guinea-pig ileum in the absence and in the presence of atropine.

Abstract

1. Slow peristalsis (less than one peristaltic wave/min) was induced by continuous elevation of intraluminal pressure in vascularly perfused segments of the guinea-pig isolated ileum. The intraluminal pressure at the aboral side of the segment and the volume of fluid propelled by each peristaltic wave were recorded. 2. Intraarterial infusion of substance P (11.5–115 pmoles min−1), cholecystokinin octapeptide (CCK-8; 1.5–15 pmoles min−1), bombesin (1–10 pmoles min−1), and neurotensin (3.6–36 pmoles min−1) dose-dependently stimulated peristalsis, the degree of stimulation being largest with CCK-8. Histamine, a drug contracting the smooth muscle directly, did not stimulate peristalsis. 3. Atropine (1 μM in the bath and perfusion solution) caused a transient inhibition or blockade of the peristaltic reflex, followed by a partial recovery of peristalsis (“atropine-resistant peristalsis”). Atropine-resistant peristalsis was greatly stimulated by CCK-8 (6–15 pmoles min−1), only slightly stimulated by bombesin (4 pmoles min−1), and first stimulated and then inhibited by neurotensin (36 pmoles min−1). 4. Substance P (11.5–1,000 pmoles min−1) inhibited or abolished atropine-resistant peristalsis, which was probably due to desensitization of intestinal smooth muscle and/or neurones against the peptide. [d-Pro2, d-Trp7,9] substance P, an analogue of substance P with antagonistic properties (40 nmoles min−1), also inhibited atropine-resistant peristalsis. 5. Naloxone (4.6 nmoles min−1) stimulated peristalsis both in the absence and in the presence of atropine; this indicates that endogenous opioids modulate peristaltic motility. 6. It is concluded that neuropeptides stimulate peristalsis by exciting intramural cholinergic and non-cholinergic neurones. The inhibitory actions of substance P desensitization and of the substance P antagonist in the presence of atropine indicate that substance P neurones play a role in the mechanism af the atropine-resistant peristalsis.