Bile secretion of sulfated glycolithocholic acid is required for its cholestatic action in rats.
To test our hypothesis that the cholestatic action of sulfated glycolithocholic acid (SGLC) in the rat is related to its interaction with calcium in the biliary tree [R. van der Meer, R. J. Vonk, and F. Kuipers. Am. J. Physiol. 254 (Gastrointest. Liver Physiol. 17): G644-G649, 1988], we have now compared its effects on bile formation in control Wistar rats and mutant Groningen Yellow (GY) Wistar rats. Intravenous injection of 0.6 mumol/100 g body wt of [14C]SGLC in unanesthetized rats with permanent biliary drainage did not induce cholestasis in either of the strains; however, its biliary secretion was strongly impaired in GY rats (12% dose at 1 h after injection vs. 95% dose in controls). Injection of 6.0 and 12.0 mumol/100 g body wt of [14C]SGLC caused an almost complete cessation of bile flow in control rats within 3 and 1 h, respectively. In contrast, administration of the same doses did not cause cholestasis in GY rats. Cholestasis in control rats was preceded by coprecipitation of [14C]SGLC and calcium in bile and incomplete biliary recovery of radioactivity. The hepatic content 15 min after injection of [14C]SGLC (6.0 mumol/100 g body wt) was similar in control and GY rats, 51 and 49% of the dose, respectively. Administration of glycolithocholic acid, the unsulfated parent compound of SGLC (6.0 mumol/100 g body wt), induced a rapid but reversible cessation of bile flow in both controls and GY rats; in this case no precipitation was observed in bile. This study shows that rapid bile secretion of SGLC is required for the induction of cholestasis.(ABSTRACT TRUNCATED AT 250 WORDS)
Kuipers
F
F
Department of Pediatrics, University of Groningen, The Netherlands.
Hardonk
M J
MJ
Vonk
R J
RJ
van der Meer
R
R
D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000032:analysis; D002779:Cholestasis; D003593:Cytoplasm / Q000648:ultrastructure; D006000:Glycocholic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000378:metabolism; D008095:Lithocholic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D014617:Vacuoles / Q000648:ultrastructure
C018154:sulfolithocholylglycine; D008095:Lithocholic Acid; D006000:Glycocholic Acid; C027746:glycolithocholic acid; D002118:Calcium