Reflex peristalsis in the guinea pig isolated ileum is endogenously controlled by kappa opioid receptors.
(1) Reflex peristalsis in the circular muscle of the guinea pig ileum was elicited in vitro by sustained luminal distension of the intestinal wall according to 2 cm H2O and evaluated in terms of the number of peristaltic waves within 15 min intervals. (2) The poorly mu-selective opioid antagonist naloxone at concentrations of 10(-7) and 10(-6) mol/l increased the frequency of peristaltic contractions within the first 15 min interval, and thereafter in a declining fashion, by 68 and 88%, respectively. The highly kappa-selective opioid antagonist nor-binaltorphimine behaved similarly. It was, by one order of magnitude, more potent but a little less effective than naloxone, i.e., the maximum effect was 57% increase in peristaltic frequency at 10(-8) mol/l. Concentrations of 10(-7) and 10(-6) mol/l had the same effect as 10(-8) mol/l, and 10(-9) mol/l were ineffective. The highly mu-selective antagonist CTOP-NH2 and the highly delta-selective antagonist ICI 174,864 were ineffective up to 10(-6) mol/l. (3) It is concluded that predominantly kappa opioid receptors are used by endogenous opioids under the present conditions to inhibit reflex peristalsis.
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Byk Gulden Pharmaceuticals, Department of Pharmacology, Konstanz, Federal Republic of Germany.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000502:physiology*; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010528:Peristalsis / Q000187:drug effects / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D009270:Naloxone; C051844:norbinaltorphimine; D013004:Somatostatin; D004743:Enkephalin, Leucine; D009271:Naltrexone; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine