Lack of tolerance of morphine-induced spasm of guinea pig sphincter of Oddi.
To determine whether guinea pigs chronically exposed to morphine would develop tolerance to the morphine-induced contraction of the sphincter of Oddi (SO), adult male guinea pigs were implanted with morphine pellets (100 mg morphine). The effect of increasing IV doses of morphine on the SO was assessed by determining the duration of which saline perfusate stopped flowing into the duodenum of morphine-treated guinea pigs (MTGP) vs nonimplanted animals (non-MTGP). Isolated bovine and guinea pigs SO were also challenged with morphine. In the in vivo experiments the spasmogenic response of the SO from MTGP to morphine was greater than that of SO from non-MTGP. However, morphine had no effect on isolated SO. These results indicate that chronic morphine exposure does not result in tolerance of the SO to the spasmogenic effects of morphine. On the contrary, chronic morphine even sensitized the SO to morphine, in addition, the in vitro data indicated that morphine does not act directly on the smooth muscle of SO to cause its spasmogenic effect.
D014670:Ampulla of Vater / Q000187:drug effects*; D000818:Animals; D003137:Common Bile Duct Diseases / Q000139:chemically induced; D004361:Drug Tolerance; D006168:Guinea Pigs; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D013035:Spasm / Q000139:chemically induced*; D009803:Sphincter of Oddi / Q000187:drug effects*
D009020:Morphine