Indirect intestinal stimulatory effects of heroin: direct action on opiate receptors

The effects of bolus intra-arterial doses of heroin and other stimulant drugs were studied in vascularly perfused isolated segments of dog small intestine. Heroin caused dose-related increases in intraluminal pressure similar in appearance to those caused by morphine. Perfusion with Krebs bicarbonate solution containing naloxone selectively abolished intestinal responses to heroin. Perfusion with cinanserin, a 5-hydroxytryptamine (5-HT) antagonist, decreased intestinal responses to 5-HT and heroin without affecting responses to dimethylphenylpiperazinium (DMPP) or bethanechol (BeCh). Tetrodotoxin reduced responses to heroin, 5-HT and DMPP but not responses to BeCh. Atropine antagonized contractile responses to all 4 stimulatory agents. These data indicate that heroin interacts with a conventional opiate receptor in the intestine and that the intestinal stimulatory effect of heroin is mediated by the release of endogenous 5-HT which activates intramural cholinergic neurons.