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MUCOSAL BIOLOGY

Bile acid-induced secretion in polarized monolayers of T84 colonic epithelial cells: structure-activity relationships

¹Division of Gastroenterology, Department of Medicine, University of California, San Diego, California; and ²Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland

Submitted 21 February 2006 ; accepted in final form 3 August 2006

Bile acid epimers and side-chain homologues are present in the human colon. To test whether such bile acids possess secretory activity, cultured T84 colonic epithelial cells were used to quantify the secretory properties of synthetic epimers and homologues of deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). In our study, chloride secretion was measured as changes in short-circuit current (I_sc, in µA/cm²) with the use of voltage-clamped monolayers of T84 cells mounted in Ussing chambers. Bile acids were added at 0.5 mM, a concentration that did not alter transepithelial resistance. Data were expressed as peak I_sc (means ± SD). When added bilaterally, DCA stimulated a I_sc response of 15.7 ± 12.5 µA/cm². The 12-OH epimer of DCA was less potent (I_sc = 8.0 ± 1.7 µA/cm²), whereas its 3-OH epimer had no effect. CDCA stimulated secretion (I_sc = 8.2 ± 5.5 µA/cm²), whereas both its 7-OH and 3-OH epimers were inactive, as was lithocholic acid. HomoDCA (1 additional side-chain carbon) was active (I_sc = 7.8 ± 4.8 µA/cm²), whereas norDCA (1 fewer carbon) and dinorDCA (2 fewer carbons) were not. Taurine conjugates of DCA and CDCA stimulated secretion (I_sc = 12.3 ± 7.5 and 8.8 ± 4.8 µA/cm², respectively) from the basolateral side but not the apical side. Uptake of taurine conjugates from the basolateral but not the apical side was shown by mass spectrometry. These studies indicate marked structural specificity for bile acid-induced chloride secretion and show that modification of bile acid structure by colonic bacteria modulates the secretory properties of these endogenous secretagogues.

bile acid homologues; conjugated bile acids; bile acid physiology

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