Opioid peptides inhibit intestinal transit in the rat by a central mechanism

Opiates and opioid peptides can alter gastrointestinal motility and delay transit of intraluminal contents. These experiments were designed to characterize the effects of beta-endorphin and [D-Ala2,Met5]enkephalinamide (DALA) on small intestinal transit in the rat. Rats were implanted with a polyethylene cannula in the right lateral cerebral ventricle and a silastic cannula in the proximal duodenum. Drugs were administered via the cerebral cannula or intraperitoneally (i.p.) Interstitial transit was assessed by instilling radiochromium into the duodenum and calculating the geometric center of the distribution of marker in the small intestine. beta-Endorphin and DALA produced a dose-related decrease in intestinal transit when the peptides were given intracerebroventricularly (i.c.v.) however, neither peptide was effective when i.p. [D-Ala2,Leu5]enkephalinamide and dynorphin-(1-13) did not alter intestinal transit. The inhibitory effects of beta-endorphin and DALA were antagonized by pretreatment with naloxone or naltrexone. A quaternary amine containing opiate antagonist. N,N-diallylnormorphinium given i.p. did not alter the response to either peptide but was effective in blocking the antitransit effects of i.p. loperamide, a peripherally acting opioid agonist. In addition, DALA reduced the body weight loss produced by castor oil-induced diarrhea while beta-endorphin had no effect. These results indicate that opioid peptides can alter intestinal motility by an action within the central nervous system. While DALA and beta-endorphin produce quantitatively the same effects on small intestinal motility, qualitatively they may differ in their mechanisms of action.