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 potential for PGE, to modulate the sensitivity of intestinal afferents. Methods: Electrophysiologic recordings were obtained from mesenteric afferent supplying the proximal jejunum of anesthetized rats. Results: PGE, evoked a dose-dependent increase in afferent nerve discharge that was biphasic at higher 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 intestinal pressure of 4.4 +/- 0.5 cm H2O. Nifedipine (1 mg (.) kg(-1)) attenuated the pressure response and the plateau phase of afferent discharge, whereas the early component remained unchanged. In contrast, the early phase, but not the plateau phase, was reduced by luminal anesthetic. Experiments with 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.