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Journal of Pharmacology And Experimental Therapeutics, Vol. 176, Issue 2, 273-283, 1971
Copyright © 1971 by American Society for Pharmacology and Experimental Therapeutics


HEPATIC AND RENAL EXCRETORY METABOLISM OF BILE SALTS: A BACKGROUND FOR UNDERSTANDING STEROID-INDUCED CHOLESTASIS

AGAMEMNON DESPOPOULOS 1

1 Royal College of Agriculture, Uppeala, Sweden; Department of Physiology, School of Medicine, University of New Mexico, Albuquerque, New Mexico

Excretory physiology of bile salts in liver and kidney was examined. In the chicken, tabular excretion of bile salts could not be established; nevertheless, all of the bile salts used inhibited tubular excretion both of phenolsulphonphthalein and of N-methylnicotinamide. Several bile salts inhibited excretion of phenolsulphonphthalein more than of N-methylnicotinamide. In surviving slices of rabbit kidney cortex, active accumulation of 4-aminohippurate was inhibited by bile salts, but the order of inhibitory potency was different from that in the chicken. In isolated perfused rat livers, taurocholate was concentrated in bile by a process which was sensitive to inhibition by probenecid. In the same system, infused cholate was excreted exclusively as taurocholate. These data furnish a background for understanding hepatic and renal excretory mechanisms for bile salts and for examining the effects of several steroidal hormones on bile salt excretion by the liver. None of the steroids interfered with taurocholate excretion nor with conversion of cholesterol to cholate, but they did inhibit synthesis of taurocholate from cholate. This influence on a fundamental reaction in the process of bile formation may account for the choleetasis which steroids have been observed to produce in a clinical setting.

Submitted on August 11, 1969
Accepted on August 28, 1970







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Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics.