Cyclic AMP-mediated chloride secretion is induced by prostaglandin F2α in human isolated colon

Background and purpose: Prostaglandin F-2 alpha (PGF(2 alpha)) is implicated in the pathogenesis of inflammatory bowel disease and colorectal cancer. This study investigates the effects of PGF(2 alpha) 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(2 alpha) stimulated chloride secretion in a concentration-dependent manner with an EC50 of 130 nM. The PGF(2 alpha) induced increase in chloride secretion was inhibited by AL8810 (10 mu M), a specific PGF(2 alpha) receptor antagonist. In addition, PGF(2 alpha) (1 mu M) significantly increased levels of cAMP in isolated colonic crypts. Conclusions and implications: PGF(2 alpha) stimulated chloride secretion in samples of human colon in vitro through a previously unrecognizd cAMP-mediated mechanism. These findings have implications for inflammatory states.