INHIBITION OF STIMULATED FLUID SECRETION IN THE RAT SMALL AND LARGE-INTESTINE BY OPIATE AGONISTS

1. The influence of morphine, levorphanol, dextrorphan, loperamide and naloxone on the increase in intestinal fluid volume (IFV) caused by PGE1, vasoactive intestinal peptide (VIP), carbachol and bethanechol was investigated in the small intestine of rats. 2. Morphine reduced the basal IFV and the increase in IFV caused by PGE1, VIP and carbachol. The effect of bethanechol was not altered by morphine. 3. The effects of levorphanol were comparable to those of morphine, whereas dextrorphan was inactive. 4. Loperamide reduced the increase in IFV caused by PGE1, but not that caused by carbachol. 5. Naloxone enhanced the effect of PGE1 and VIP on IFV but neither altered basal IFV nor the effect of carbachol. This result may suggest an inhibitory influence of intestinal enkephalins on PGE1-or VIP-induced intestinal secretion. 6. The influence of opiates was further tested on the effect of the diphenolic laxative, bisacodyl and of the osmotic laxative, mannitol on water net flux in the tied off colon of the rat in situ. Morphine, levorphanol and loperamide reduced the effect of bisacodyl, whereas the effect of mannitol and the net water absorption in controls remained unchanged. 7. The experiments show an antisecretory effect of opiates on different types of stimulation of fluid secretion in the small and large intestine. It is concluded that the antidiarrhoeal action of opiates can be better explained by antisecretory than by smooth muscle action on the gut. © 1979 Springer-Verlag.