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Increased Canalicular Bile Production Induced by Pregnenolone-16α-Carbonitrile, Spironolactone and Cortisol in Rats

Summary In the rat, pregnenolone-16α-carbonitrile (PCN), spironolactone, and cortisol increased bile flow by 88, 49, and 41%, respectively. The total biliary bile salt excretion rates ran parallel in control and steroid-treated animals, indicating that enhanced biliary secretion is not due to osmotic choleresis caused by augmented bile salt elimination. 14C-Erythritol clearance studies demonstrate that the steroid-induced increase of bile flow is of canalicular origin. The correlation between estimated canalicular bile flow and biliary bile salt excretion reveals that PCN accelerates biliary flow by significantly enhancing the bile-salt independent fraction of canalicular bile. The effect of spironolactone and cortisol is similar but less pronounced than that of PCN. This work was supported in part by grants awarded to the Institut de Médecine et de Chirurgie Experimentales by the Medical Research Council of Canada (Block Term Grant MT-1829), Succession J. A. DeSève, and the Colonial Research Institute, Freeport, Bahamas. The authors thank the Companies listed in the Methods section for the compounds used in this study.