Cerebral delta opioid receptors mediate analgesia but not the intestinal motility effects of intracerebroventricularly administered opioids.
Conformationally constrained cyclic enkephalin analogs which possess a high selectivity for the delta opioid receptor were used to determine the relative contribution of mu and delta receptors to brain-mediated changes in small intestinal propulsion and increases in hot-plate response time. Receptor preferences were determined by comparing the relative potencies of several opioid agonists in suppressing the electrically evoked contractions of the guinea-pig ileum and mouse vas deferens preparations. The ratio of IC50 values obtained in the guinea-pig ileum and the mouse vas deferens was used as an index of delta receptor selectivity. Effects on intestinal transit were determined in rats in which a silastic cannula had been implanted in the proximal duodenum and a polyethylene cannula in the right lateral cerebral ventricle (i.c.v.). Movement of a radioactive marker along the length of the small intestine after instillation into the duodenum was used to evaluate drug-induced changes in intestinal transit. The analgesic effects of i.c.v. administered opioids were determined in a second group of rats in which i.c.v. cannulas alone had been implanted. After i.c.v. administration of the agonist, the rats were placed on a 55 degrees C hot plate and the latency to rear paw-lick was timed. Compounds which showed a preference for the mu receptor [( D-Ala2, N-methyl-Phe4, Gly5 -ol]enkephalin and morphine/normorphine) were the most potent agonists at producing thermal analgesia and inhibition of small intestinal transit, whereas nonselective compounds (beta-endorphin and [D-Ala2, Met5]enkephalinamide) were slightly less potent in these assays.(ABSTRACT TRUNCATED AT 250 WORDS)
D000698:Analgesia; D000818:Animals; D001681:Biological Assay; D001921:Brain / Q000187:drug effects*; D004745:Enkephalins / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006358:Hot Temperature; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects
D004745:Enkephalins; D009294:Narcotics; D011957:Receptors, Opioid