RT Journal Article
SR Electronic
T1 MEDIATION BY 5-HYDROXYTRYPTAMINE OF MORPHINE STIMULANT ACTIONS IN DOG INTESTINE
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 530
OP 539
VO 185
IS 3
A1 THOMAS F. BURKS
YR 1973
UL http://jpet.aspetjournals.org/content/185/3/530.abstract
AB Intestinal contractor effects of morphine, 5-hydroxytryptamine (5-HT) and cholinergic agonists were investigated in sections of dog small intestine perfused in vitro with Krebs' solution. Morphine and 5-HT produced similar patterns of intestinal hypermotility characterized by initial tonic increases in intraluminal pressure and pronounced secondary phasic contractions. The morphine-induced hypermotility could not have resulted from extrinsic influences on the isolated segments of bowel. Cholinergic agonists generally produced only brief tonic contractions of the intestinal smooth muscle. Treatment of dogs with reserpine to deplete local stores of 5-HT selectively reduced intestinal responses to morphine. This indicated that release of endogenous 5-HT initiates the spasmogenic response to the narcotic. The contractor effects of 5-HT and morphine were diminished by tetrodotoxin, nicotine depolarization and atropine but not by tetraethylammonium These data demonstrate that a significant portion of the stimulatory action of the 5-HT released by morphine results from activation of intramural cholinergic nerve elements which differ from those activated by conventional ganglionic stimulants. Experiments with the 5-HT receptor blocking drugs, cinanserin and cyproheptadine, indicate that the 5-HT mobilized by morphine also exerts direct stimulatory actions on smooth muscle 5-HT receptors. The hypermotility of the dog bowel induced by morphine thus appears to result from release of local intestinal 5-HT. The 5-HT liberated by morphine exerts both direct and indirect excitatory smooth muscle effects. The indirect component of 5-HT action is mediated by cholinergic nerve elements in the wall of the intestine. © 1973 by The Williams & Wilkins Co.