Cyclic AMP-mediated chloride secretion is induced by prostaglandin F 2α in human isolated colon

Abstract

Background and purpose: Prostaglandin F 2α (PGF 2α) is implicated in the pathogenesis of inflammatory bowel disease and colorectal cancer. This study investigates the effects of PGF 2α on electrophysiological parameters in isolated human colonic mucosa. Experimental approach: Ion transport was measured as changes in short-circuit current across human colonic epithelia mounted in Ussing chambers. Colonic crypts were isolated by calcium chelation and cyclic adenosine monophosphate (cAMP) was measured by ELISA. Key Results: PGF 2α stimulated chloride secretion in a concentration-dependent manner with an EC 50 of 130 nM. The PGF 2α induced increase in chloride secretion was inhibited by AL8810 (10 μM), a specific PGF 2α receptor antagonist. In addition, PGF 2α (1 μM) significantly increased levels of cAMP in isolated colonic crypts. Conclusions and implications: PGF 2α stimulated chloride secretion in samples of human colon in vitro through a previously unrecognizd cAMP-mediated mechanism. These findings have implications for inflammatory states. © 2009 The British Pharmacological Society.