Ursodeoxycholic acid attenuates colonic epithelial secretory function

摘要: Dihydroxy bile acids, such as chenodeoxycholic acid (CDCA), are well known to promote colonic fluid and electrolyte secretion, thereby causing diarrhoea associated with malabsorption. However, CDCA is rapidly metabolised by bacteria ursodeoxycholic (UDCA), the effects of which on epithelial transport poorly characterised. Here, we investigated role UDCA in regulation secretion. Cl(-) secretion was measured across voltage-clamped monolayers T84 cells muscle-stripped sections mouse or human colon. Cell surface biotinylation used assess abundance/surface expression proteins. Acute (15 min) treatment bilateral attenuated secretory responses Ca(2+) cAMP-dependent secretagogues carbachol (CCh) forskolin (FSK) 14.0 ± 3.8 40.2 7.4% controls, respectively (n = 18, P < 0.001). Investigation molecular targets involved revealed that acts inhibiting Na(+)/K(+)-ATPase activity basolateral K(+) channel currents, without altering their cell expression. In contrast, intraperitoneal administration (25 mg kg(-1)) mice enhanced agonist-induced responses, an effect hypothesised be due bacterial metabolism lithocholic (LCA). Accordingly, LCA (50-200 μm) vitro a metabolically stable analogue, 6α-methyl-UDCA, exerted anti-secretory actions vivo. conclusion, exerts direct derivatives may offer new approach for treating intestinal diseases diarrhoea.