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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

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Summary

  1. 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. 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. 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. 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. 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. 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.

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Authors and Affiliations

  1. Department of Experimental and Clinical Pharmacology, Universitätsplatz 4, A-8010, Graz, Austria

    L. Barthó, P. Holzer, J. Donnerer & F. Lembeck

  2. Pain Research Commission of the Austrian Academy of Sciences, Universitätsplatz 4, A-8010, Graz, Austria

    L. Barthó, P. Holzer, J. Donnerer & F. Lembeck

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  1. L. Barthó
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  2. P. Holzer
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  3. J. Donnerer
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  4. F. Lembeck
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Barthó, L., Holzer, P., Donnerer, J. et al. 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. Naunyn-Schmiedeberg's Arch. Pharmacol. 321, 321–328 (1982). https://doi.org/10.1007/BF00498521

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  • DOI: https://doi.org/10.1007/BF00498521

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