Influence of Opiates on Ion Transport Across Rabbit Ileal Mucosa

Opiates are commonly used as antidiarrheal agents, and endogenous opioids have been demonstrated in the intestine. It seemed important therefore to investigate the effects of morphine on ion transport across intestinal mucosa. In rabbit ileum in vitro morphine (2 x 10(-5) M) induced a significant fall in potential difference and short circuit current but did not influence tissue resistance. Dextromoramide (10(-5) M), an active opiate, mimicked the action of morphine, whereas the inactive isomer levomoramide (10(-5) M) had no effect. Morphine caused a significant increase in chloride absorption, due predominantly to a decrease in the serosa to mucosa flux. No change in sodium transport was detected, but the residual ion flux, possibly representing bicarbonate secretion, was enhanced. Similar response were observed with a synthetic enkephalin analogue (Me-Tyr-D-Met-Gly-Phe-Pro-NH2); but this was more potent than morphine, a significant electrical response being observed at a concentration as low as 10(-8) M. These electrical and ion transport responses to morphine were blocked by naloxone, an effect shown to be competitive in nature. The results suggest that opiate receptors exist in rabbit ileal mucosa and that these influence electrical and ion transport changes across the mucosa.