MAST-CELLS AND HISTAMINE CONTRIBUTE TO BILE ACID-STIMULATED SECRETIONIN THE MOUSE COLON

Certain dihydroxy bile acids cause secretory diarrhea when present in the colonic lumen at inappropriately high concentrations. However, the mechanism underlying the secretagogue activity has not been fully elu cidated. Experiments were performed to test whether mast cells and one of their major mediators, histamine, might contribute to the secretor y effect. Chenodeoxycholic acid, a secretory bile acid, and ursodeoxyc holic acid, a nonsecretory, hydrophilic bile acid, were compared for t heir ability to induce chloride secretion across segments of mouse col on mounted in Ussing chambers. Chenodeoxycholic acid, but not ursodeox ycholic acid, induced dose-dependent, biphasic chloride secretion that was greater after serosal than mucosal addition and was greater in di stal versus proximal colonic segments. The secretory effect of chenode oxycholic acid was inhibited by H-1 histamine receptor antagonists and modified by the cyclooxygenase inhibitor indomethacin. However, it wa s unaffected by an H-2 histamine receptor antagonist or by atropine, S ecretory effects of chenodeoxycholic acid were diminished in magnitude and delayed in colonic tissues from mice with a genetic deficiency of tissue mast cells. Concentrations of chenodeoxycholic acid inducing s ecretion also released histamine from tissue segments. These data indi cate that mast cells and histamine-mediated processes contribute signi ficantly to the secretory effects of dihydroxy bile acids in the murin e colon.