title: Bile secretion of sulfated glycolithocholic acid is required for its cholestatic action in rats.
abstract: 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)
authors.affiliation: Department of Pediatrics, University of Groningen, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Kuipers
authors.forename: M J
authors.initials: MJ
authors.lastname: Hardonk
authors.forename: R J
authors.initials: RJ
authors.lastname: Vonk
authors.forename: R
authors.initials: R
authors.lastname: van der Meer
mesh_terms: 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
chemical_list: C018154:sulfolithocholylglycine; D008095:Lithocholic Acid; D006000:Glycocholic Acid; C027746:glycolithocholic acid; D002118:Calcium