Colonic secretion mediated by prostaglandin E2 and 5-hydroxytryptamine may contribute to diarrhea due to morphine withdrawal in the rat.
Prostaglandins and cyclic adenosine monophosphate have been claimed to play a major role in the morphine withdrawal syndrome, but intestinal secretion has not been ruled out as being responsible, at least in part, for the accompanying diarrhea. Therefore, experiments were performed in which the effect of naloxone-induced morphine withdrawal on jejunal and on colonic fluid transport was assessed in tied-off loops of rat intestine in vivo simultaneously with mucosal cyclic adenosine monophosphate levels or colonic luminal release of prostaglandin E2 or 5-hydroxytryptamine. Naloxone-induced withdrawal reversed fluid absorption to secretion without changing cyclic adenosine monophosphate levels, but markedly enhanced local prostaglandin E2 and 5-hydroxytryptamine release (p less than 0.01). Indomethacin and the 5-hydroxytryptamine receptor antagonist ketanserin prevented withdrawal-induced fluid secretion and the increase in prostaglandin E2 release without influencing the release of 5-hydroxytryptamine. In addition, the alpha 2-adrenergic receptor agonist clonidine promoted absorption during withdrawal, whereas atropine failed to influence fluid transport. These data suggest that naloxone-precipitated intestinal fluid secretion may contribute to diarrhea due to morphine withdrawal and that 5-hydroxytryptamine may play an important role in mediating this secretion through stimulation of local prostaglandin formation.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D003967:Diarrhea / Q000139:chemically induced* / Q000503:physiopathology; D015232:Dinoprostone; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007650:Ketanserin; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011458:Prostaglandins E / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced / Q000503:physiopathology*
D010880:Piperidines; D011458:Prostaglandins E; D012701:Serotonin; D009270:Naloxone; D001285:Atropine; D007650:Ketanserin; D000242:Cyclic AMP; D015232:Dinoprostone; D003000:Clonidine; D007213:Indomethacin