Inhibition by morphine of prostaglandin-stimulated fluid secretion in rat jejunum.
1 Anesthetized rats (225 to 300 g) were used to study the inhibitory effect of morphine on fluid secreted by the small intestine. 2 Small intestinal fluid secretion was stimulated by infusion of prostaglandin E1 (PGE1) into the aortic arch, the jejunum being more sensitive than the ileum. Infusion of PGE1 2 microgram/min caused maximal net fluid secretion in the jejunum but inhibited net fluid absorption in the ileum. 3 Morphine caused a dose-related inhibition of maximal PGE1-stimulated fluid secretion in the jejunum. At the higher doses of morphine used (5 to 20 mg/kg) the fluid transporting function of the jejunum was restored almost to normal net absorption. 4 The inhibitory effect of morphine on PGE1-stimulated fluid secretion was antagonized by naloxone. Naloxone caused a parallel shift to the right of the dose-response curve for morphine. 5 Two other narcotic analgesics were assayed relative to morphine and their descending order of potency was oxymorphone greater than morphine greater than pethidine. 6 It is suggested that the antisecretory effect of morphine in the small intestine may contribute to its efficacy as an anti-diarrhoeal drug. Further studies on the rat jejunum may show it to be a useful model for predicting narcotic drug activity and as such, may give some insight into the mechanisms of action of these drugs.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007082:Ileum / Q000187:drug effects; D007408:Intestinal Absorption / Q000187:drug effects; D007419:Intestinal Secretions / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects; D008297:Male; D008614:Meperidine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010111:Oxymorphone / Q000494:pharmacology; D011458:Prostaglandins E / Q000037:antagonists & inhibitors*; D051381:Rats
D011458:Prostaglandins E; D009270:Naloxone; D009020:Morphine; D008614:Meperidine; D010111:Oxymorphone