16,16-DIMETHYL PROSTAGLANDIN-E2 INDUCES VILLUS CONTRACTION IN RATS WITHOUT AFFECTING INTESTINAL RESTITUTION

In a previous study we found that 16,16-dimethyl prostaglandin E2 protects the small intestine against chenodeoxycholic acid injury in the rat. One possible explanation for prostaglandin's protective action may be that prostaglandin-induced villus contraction accelerates mucosal restitution. This hypothesis was tested in rats by perfusing intestinal segments in vivo in a single-pass fashion with 0.125-0.5 μg/L of 16,16-dimethyl prostaglandin E2. These studies showed a dose-dependent, reversible contraction of intestinal villi and crypts. To test the effect of this contraction on mucosal restitution, standardized intestinal injury was produced in indomethacin-pretreated rats perfused in vivo with 5 mmol/L chenodeoxycholic acid. The rats were then perfused with bile acid-free buffer containing either 0.5 μg/mL of 16,16-dimethyl prostaglandin E2 or vehicle. This study showed that despite decreasing villus height after bile acid injury, 16,16-dimethyl prostaglandin E2 did not significantly affect the rate of morphologic (assessed by villus denudation) or functional (assessed by mannitol and water absorption) restitution of the injured intestinal mucosa. Thus, although 16,16-dimethyl prostaglandin E2 causes villus contraction, this effect does not result in more rapid restitution of the injured intestinal mucosa and is not a likely mechanism for prostaglandin-mediated protection of the intestinal mucosa. © 1990.