Johnson E E
J Pharmacol Exp Ther. 1981 Oct;219(1):274-80.
The effects of i.v. bolus injections of morphine sulfate on resistance to flow through the choledochoduodenal junction were studied in acutely prepared dogs anesthetized with pentobarbital. Dose-response studies indicate that the spasmogenic effect of 0.1 mg/kg of morphine is greater than that of 1.0 mg/kg of morphine. These and other data indicate a combination of stimulatory and inhibitory activity with the relaxing activity occurring at higher doses. Inhibitory activity was potentiated by neostigmine, given 1 hr before morphine. Prior administration of atropine or vagotomy enhanced the stimulatory effect, possibly by blockade of the inhibitory effect. Vagotomy did not block the inhibitory effect of morphine in dogs pretreated with neostigmine. After three serial injections of 1.0 mg/kg, of morphine, naloxone challenge elicited strong choledochoduodenal contractions in reserpine-treated dogs, neostigmine-treated dogs and dogs given 0.1 mg/kg of morphine 1 hr before 1.0 mg/kg of morphine. In dogs pretreated with neostigmine, contractions upon naloxone challenge were always completely blocked by atropine. Acetylcholine release may be involved in the inhibitory effect of morphine at the canine choledochoduodenal junction.