INHIBITION BY MORPHINE OF PROSTAGLANDIN‐STIMULATED FLUID SECRETION IN RAT JEJUNUM

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Abstract
Anaesthetized rats (225 to 300 g) were used to study the inhibitory effect of morphine on fluid secreted by the small intestine. 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 μg/min caused maximal net fluid secretion in the jejunum but inhibited net fluid absorption in the ileum. 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. 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. Two other narcotic analgesics were assayed relative to morphine and their descending order of potency was oxymorphone < morphine > pethidine. 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.