EFFECT OF NEUROPEPTIDES ON THE EFFICIENCY OF THE PERISTALTIC REFLEX

1. A peristaltic reflex preparation of the isolated guinea-pig ileum was developed which had an intact vascular supply and into which drugs were infused intraarterially. Intraluminal pressure and intraluminal volume propelled per time were recorded. Peristalsis was triggered by raising the intraluminal pressure at constant time intervals. 2. Caerulein (>0.2 pmoles min-1), substance P (>5 pmoles min-1), 5-hydroxytryptamine (>90 pmoles min-1), and bethanechol (>900 pmoles min-1) initiated peristalsis when intraluminal pressure was not raised. 3. Under conditions of isotonic longitudinal contraction pressure-induced peristalsis was reduced by substance P and bethanechol, but not affected by caerulein and 5-hydroxytryptamine. 4. Under conditions of isometric longitudinal contraction, caerulein (0.5 pmoles min-1), substance P (2.4 pmoles min-1), 5-hydroxytryptamine (180 pmoles min-1), and bethanechol (355 pmoles min-1) increased the efficiency of the peristaltic reflex. 5. d-Ala2-d-met5-enkephalin (>27 pmoles min-1) and d-ala2-mephe4-met-(O)5-ol-enkephalin (FK 33-824, >11 pmoles min-1) inhibited the peristaltic reflex, thus exceeding the potency of morphine, atropine, noradrenaline, hexamethonium, and isoprenaline 100-1000-fold. 6. ATP, 13-nle-motilin, somatostatin, and vasoactive intestinal polypeptide had no influence on the peristaltic reflex. 7. Since substance P and enkephalin are the most potent compounds of mammalian origin in affecting peristalsis it is concluded that they are involved in the nervous mechanisms of the peristaltic reflex. © 1979 Springer-Verlag.