Selective antagonism of the intesinal stimulatory effects of morphine by isoproterenol prostalglandin E1 and theophylline.

Contractions induced by graded intraaterial bolus doses of morphine and acetylcholine were measured in isolated segments of dog intestine perfused via the vasculature with Kreb's solution. Addition of the alpha and beta adrenergic receptor agonist, norepinephrine (0.2 mug/ml) to the perfusion solution decreased the magnitude of contractor responses to acetylcholine slightly and to morphine considerably. The pure alpha adrenergic receptor agonist, methoxamine (50 mug/ml), and the pure beta adrenergic receptor agonist, isoproterenol (5 mug/ml), produced similar effects; marked inhibition of responses to morphine and barely discernable inhibition of responses to acetylcholine. The mild inhibitory effects of these adrenergic amines on responses to acetylcholine are attributed to actions on neural and possibly non-neural adrenergic receptors. Perfusion of intestinal segments with Kreb's solution containing prostaglandin E1 (1 mug/ml) or theophylline (180 mug/ml) resulted in marked decreases in responses to morphine but had no significant effects on responses to acetylcholine. Patterns of inhibition similar to those seen with morphine have been observed previously with 5-hydroxytryptamine, which may mediate the intestinal stimulatory effects of morphine. Since isoproterenol, prostaglandin E1 and theophylline share in common the ability to elevate or maintain intracellular levels of cyclic adenosine monophosphate, the intestine stimulatory effects of morphine may result from 5-hydroxytryptamine-mediated interference with smooth muscle inhibitory actions of cyclic adenosine monophosphate.