Deoxycholic acid (DOC) affects the transport properties of distal colon

Secondary bile acids can induce diarrhea. In the present study we examined the effects of deoxycholic acid (DOC) on equivalent short-circuit current (I-sc) in rabbit colon and the cellular mechanisms involved in DOC action (rabbit and rat), Luminal DOC inhibited amiloride-sensitive Na+ absorption. In the presence of amiloride luminal DOC had a concentration dependent effect on I-sc. Low concentrations (1-10 mu mol/l) induced a lumen-positive current (51+/-3 mu A/cm(2). 10 mu mol/l, n=7) which was inhibited by luminal Ba2+ suggesting the activation of a luminal K+ conductance. Higher luminal concentrations induced a lumen-negative current (-76+/-9 mu A/cm(2) 100 mu mol/l, n=11). Basolateral application of DOG. also in the presence of amiloride, only induced lumen-negative I-sc (-58+/-10 mu A/cm(2). 100 mu mol/l, n=6, EC50 = 3 mu mol/l). This current could be abolished completely by the K+ channel blocker 293B. a selective inhibitor of cAMP-dependent Cl- secretion. This action of DOC on I-sc was additive to the effect of carbachol (CCH) but not additive to that of cAMP. In intact rat colon mucosa pre treated with DOC a significant increase in cAMP production was observed. Fura-2 measurements of cytosolic Ca2+ activity ([Ca2+](i)) in isolated colonic crypts (rabbit and rat) showed that 100 mu mol/l DOC induced a weak [Ca2+](i) increase. Whole-cell measurements of membrane voltage in isolated rat colonic crypts revealed a hyperpolarization by DOC (-4.9+/-0.8 mV. 100 mu mol/l. n=8) but a depolarization by prostaglandin E-2 (PGE(2), via cAMP) (24+/-7 mV. n=8). The present data show that DOC acts at more than one target in the colon: in the intact mucosa it activates luminal K+ channels and Cl- secretion and this is paralleled by an increase in cAMP production. In isolated crypt,, DOC probably activates a Ca2+-regulated K+ conductance but has no effect on cAMP. Hence DOC probably activates ion channels or channel-regulating factors in colonocytes and acts on non-epithelial cells to activate Cl- secretion indirectly.