Physiologic determinants of biliary calcium secretion in the dog

Abstract

Studies were carried out to define the origins and physiologic determinants of biliary calcium secretion in the dog. Canalicular bile flow was varied by infusions of several bile acids or a canalicular choleretic agent, SC2644. Three natural bile acids (cholyltaurine, chenodeoxycholyltaurine, and ursodeoxycholyltaurine) that have a low critical micellar concentration and a synthetic hydroxy-oxo bile acid (12-dehydrocholyltaurine) with a much higher critical micellar concentration were used. Calcium output, bile acid output, and bile flow were determined; canalicular bile flow was assessed by measurement of erythritol clearance. Calcium output increased linearly with bile acid output for all three natural bile acids (r = 0.94; 0.026–0.035 μmolΔcalcium /μmolΔbile acid), but chenodeoxycholyltaurine and ursodeoxycholyltaurine infusions induced a slightly greater secretion of calcium for a given bile acid output and bile flow than cholyltaurine. Calcium output also increased linearly with bile flow, whether bile flow was induced by the canalicular choleretic SC2644 (r = 0.93; 0.0018 μmolΔcalcium/ μlΔwater) or the hydroxy-oxo bile acid (r = 0.99; 0.0021 μolΔcalciumμlΔwater). Because the calcium output induced by the three micelle-forming bile acids was greater than that which could be explained by the induced increase in bile flow per se, it was deduced that canalicular calcium has two origins; a micellar component that is dependent on the presence of micelles or micelle-forming bile acids and an osmotic component that is dependent on osmotic forces, e.g., caused by secretion induced by SC2644 or bile acid molecules and possibly bile acid micelles. A small bile acid-independent output of calcium was also detected and should contribute to the osmotic fraction. To determine whether ductular modification of bile flow influenced biliary calcium secretion, ductular secretion was induced by secretin and ductular absorption was induced by somatostatin. Changes in calcium output followed water movements, increasing with ductular secretion and decreasing with ductular absorption. The relationship between changes in ductular bile flow and calcium output was identical during induced ductular secretion (r = 0.83; 0.0016 μmolΔcalcium/ μlΔwater) or induced ductular absorption (r = 0.91; 0.0019 μmolΔcalcium/μlΔwater). Thus calcium movements in relation to water movements were identical for the osmotic component of canalicular bile and the ductular component of bile. The experimental manipulations in bile secretion caused anticipated changes in biliary calcium concentration which ranged from 1.6 to 6.4 mM. These results indicate that at the usual rates of bile acid secretion, most biliary calcium originates at the canaliculus and is bile acid-dependent. The biliary ductule is permeable to calcium, but the effect of ductular modification of bile flow on biliary calcium outputs is small.