Carbachol-stimulated chloride secretion in mouse colon: evidence of a rolefor autocrine prostaglandin E-2 release

We used the short-circuit current technique to investigate the possible fac ilitatory role of epithelium-derived prostaglandin E-2 (PGE(2)) release on Cl- secretion in the mouse colon. Carbachol- (CCh)-stimulated Cl- secretion was reduced by pretreatment with either indomethacin (10 mu M), or TTX (1 mu M), and when added together, these inhibitors revealed net CCh-stimulate d K+ secretion. CCh-stimulated Cl- secretion was partially restored to TTX/ indomethacin-treated colons by addition of a subsecretory concentration of PGE(2) (1 nM). In acutely isolated, unstimulated crypt cells, we measured P GE, release at a similar level. We conclude that autocrine release of PGs f rom epithelial cells is sufficient to support the CCh-induced Cl- secretory response and is a likely co-factor in this response.