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Am J Physiol Gastrointest Liver Physiol 281: G984-G996, 2001;
0193-1857/01 $5.00
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Vol. 281, Issue 4, G984-G996, October 2001

Prostanoids stimulate K secretion and Cl secretion in guinea pig distal colon via distinct pathways

Dan R. Halm and Susan Troutman Halm

Department of Physiology and Biophysics, Wright State University, Dayton, Ohio 45435

Short-circuit current (Isc) and transepithelial conductance (Gt) were measured in guinea pig distal colonic mucosa isolated from submucosa and underlying muscle layers. Indomethacin (2 µM) and NS-398 (2 µM) were added to suppress endogenous production of prostanoids. Serosal addition of PGE2 (10 nM) stimulated negative Isc consistent with K secretion, and concentrations >30 nM stimulated positive Isc consistent with Cl secretion. PGE2 also stimulated Gt at low and high concentrations. Dose responses to prostanoids specific for EP prostanoid receptors were consistent with stimulating K secretion through EP2 receptors, based on a rank order potency (from EC50 values) of PGE2 (1.9 nM) > 11-deoxy-PGE1 (8.3 nM) > 19(R)-hydroxy-PGE2 (13.9 nM) > butaprost (67 nM) > 17-phenyl-trinor-PGE2 (307 nM) sulprostone (>10 µM). An isoprostane, 8-iso-PGE2, stimulated K secretion with an EC50 of 33 nM. Cl secretory response was stimulated by PGD2 and BW-245C, a DP prostanoid receptor-specific agonist: BW-245C (15 nM) > PGD2 (30 nM) > PGE2 (203 nM). Agonists specific for FP, IP, and TP prostanoid receptors were ineffective in stimulating Isc and Gt at concentrations <1 µM. These results indicate that PGE2 stimulated electrogenic K secretion through activation of EP2 receptors and electrogenic KCl secretion through activation of DP receptors. Thus stimulation of Cl secretion in vivo would occur either via physiological concentrations of PGD2 (<100 nM) or pathophysiological concentrations of PGE2 (>100 nM) that could occur during inflammatory conditions.

prostaglandin E2; prostaglandin D2; isoprostane; inflammation


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