Prostaglandin D2 regulates human colonic ion transport via the DP1 receptor

Aims: Prostaglandin D-2 is released by mast cells and is important in allergies. Its role in gastrointestinal function is not clearly defined. This study aimed to determine the effect of exogenous PGD(2) on ion transport in ex vivo normal human colonic mucosa. Materials and methods: Mucosal sheets were mounted in Ussing chambers and voltage clamped to zero electric potential. Ion transport was quantified as changes in short-circuit current. In separate experiments epithelial monolayers or colonic crypts, isolated by calcium chelation, were treated with PGD(2) and cAMP levels determined by ELISA or calcium levels were determined by fluorimetry. Key findings: PGD(2) caused a sustained, concentration-dependent rise in short-circuit current by increasing chloride secretion (EC50 = 376 nM). This effect of PGD(2) is mediated by the DP1 receptor, as the selective DP1 receptor antagonist BW A686C inhibited PGD(2)-induced but not PGE(2)-induced rise in short-circuit current. PGD2 also increased intracellular cAMP in isolated colonic crypts with no measurable influence on cytosolic calcium. PGD(2) induces chloride secretion in isolated human colonic mucosa in a concentration-dependent manner with concomitant elevation of cytoplasmic cAMP in epithelial cells. Significance: The involvement of DP2 receptor subtypes has not previously been considered in regulation of ion transport in human intestine. Since inflammatory stimuli may induce production of eicosanoids, selective regulation of these pathways may be pivotal in determining therapeutic strategies and in understanding disease. (C) 2014 Elsevier Inc. All rights reserved.