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 (r abbit and rat), Luminal DOC inhibited amiloride-sensitive Na+ absorption. I n the presence of amiloride luminal DOC had a concentration dependent effec t on I-sc. Low concentrations (1-10 mu mol/l) induced a lumen-positive curr ent (51+/-3 mu A/cm(2). 10 mu mol/l, n=7) which was inhibited by luminal Ba 2+ suggesting the activation of a luminal K+ conductance. Higher luminal co ncentrations induced a lumen-negative current (-76+/-9 mu A/cm(2) 100 mu mo l/l, n=11). Basolateral application of DOG. also in the presence of amilori de, 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- secretio n. 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 w ith DOC a significant increase in cAMP production was observed. Fura-2 meas urements 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) incr ease. Whole-cell measurements of membrane voltage in isolated rat colonic c rypts 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 co lon: in the intact mucosa it activates luminal K+ channels and Cl- secretio n and this is paralleled by an increase in cAMP production. In isolated cry pt,, DOC probably activates a Ca2+-regulated K+ conductance but has no effe ct on cAMP. Hence DOC probably activates ion channels or channel-regulating factors in colonocytes and acts on non-epithelial cells to activate Cl- se cretion indirectly.