Duodenal secretion in humans mediated by the EP4 receptor subtype

Abstract

Assessment of functional EP receptor subtypes involved in PGE2-induced secretion in human duodenum. The spectrum of activities by PGE2 in mammals, including cytoprotective bicarbonate secretion in duodenum, is mediated through four G protein-coupled receptor subtypes (EP1-EP4). Biopsies from the second part of duodenum from patients undergoing endoscopy were mounted in modified Ussing chambers. Basal and stimulated short circuit current (SCC) and slope conductance (SG) were measured. Dose-response relations for PGE2 and subtype receptors EP1/EP3 (sulprostone), EP2 (butaprost), and EP4 (1-OH PGE1) were assessed by cumulated doses of single agonists. PGE2 caused a dose-dependent increase in SCC, maximum 101 +/- 20 microA cm(-2) with an EC50 of 35.6 +/- 5.8 nm (n = 3). Likewise 1-OH PGE1 caused a dose-dependent SCC increase, maximum 63.3 +/- 28.6 microA cm(-2) with an EC50 of 56.7 +/- 7.2 nm (n = 3). 1-OH PGE1 at 500 nm increased SCC by 18.0 +/- 3.0 microA cm(-2) (n = 10) and SG by 2.9 +/- 0.4 mS cm(-2) (n = 6). Sulprostone (n = 6) and butaprost (n = 6) had no effects on SCC or SG. SCC was inhibited 31.4 +/- 13.2% (n = 10) by bumetanide (25 microM serosa) and 18.6 +/- 5.8% (n = 10) by acetazolamide (250 microM lumen). Diphenylamine-2-carboxylate (DPC) (250 microM mucosa) and SITS (10 microM mucosa) had almost no effect. Effects of PGE2 on secretion in the second part of human duodenum is mediated through the EP4 receptor and not through EP1, EP2, or EP3.