Characterization of calcium deprivation-induced cholestasis in the perfused rat liver.
To elucidate the role of calcium in regulation of canalicular bile flow, we studied biliary sucrose permeability and the transport kinetics of taurocholate in the in situ perfused rat liver. Calcium deprivation did not adversely affect viability or ultrastructural appearances of the liver. Removal of calcium led to initial choleresis followed by cholestasis dependent on external ionized calcium concentration. Biliary recovery of [14C]sucrose relative to that of tritiated water was determined by a biliary multiple-indicator dilution technique. Analysis in terms of irreversible thermodynamics suggested that biliary permeability to sucrose increased due to a change in the sieving coefficient from 0.135 to 0.435. Biliary recovery of taurocholate was significantly (P less than 0.001) reduced in low-calcium medium (from 79.6 +/- 6.5 to 17.6 +/- 11.8%). This was not due to a defect in hepatocellular uptake of taurocholate as determined in the perfused rat liver by a multiple-indicator dilution technique and in isolated hepatocytes. We conclude that calcium deprivation-induced cholestasis is characterized by an increased biliary permeability, a defect in cellular translocation and/or canalicular secretion of bile salts, and a defect in bile salt-independent bile flow.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001692:Biological Transport; D002118:Calcium / Q000172:deficiency* / Q000502:physiology; D002779:Cholestasis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D007365:Intercellular Junctions / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D008297:Male; D010477:Perfusion; D010539:Permeability; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism
D013395:Sucrose; D013656:Taurocholic Acid; D002118:Calcium