Prostaglandin EP receptor subtypes have distinctive effects on jejunal afferent sensitivity in the rat

Background & Aims Tissue levels of prostaglandin (PG) E-2 are increased in inflammatory bowel disease. The aim of this study was to characterize the p otential for PGE, to modulate the sensitivity of intestinal afferents. Meth ods: Electrophysiologic recordings were obtained from mesenteric afferent s upplying the proximal jejunum of anesthetized rats. Results: PGE, evoked a dose-dependent increase in afferent nerve discharge that was biphasic at hi gher doses. An early response phase, peak discharge frequency of 165.4 +/- 14.3 imp (.) s(-l), and duration of 20.2 +/- 1.2 seconds were followed by a plateau of elevated afferent nerve discharge lasting several minutes. The increase in afferent nerve discharge was accompanied by an increase in inte stinal pressure of 4.4 +/- 0.5 cm H2O. Nifedipine (1 mg (.) kg(-1)) attenua ted the pressure response and the plateau phase of afferent discharge, wher eas the early component remained unchanged. In contrast, the early phase, b ut not the plateau phase, was reduced by luminal anesthetic. Experiments wi th EP receptor-selective agonists and the EP1-receptor antagonist AH-6809 ( 500 mug (.) kg(-1)) implicate EP1 receptors in the early response, and EP, receptors appeared to play a major role in the plateau phase. Conclusions: PGE, has complex actions on intestinal afferent discharge acting by direct and indirect mechanisms and mediated by different receptor subtypes.