Browsing by Author "HONO, J"

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    ADAPTIVE REGULATION OF HEPATIC BILE-SALT TRANSPORT - EFFECT OF PROLONGED BILE-SALT DEPLETION IN THE RAT
    (1988) ACCATINO, L; HONO, J; MALDONADO, M; ICARTE, MA; PERSICO, R
    Exposure of the liver to increased bile salt flux can increase the bile salt maximum secretory rate (SRm), presumably through the induction of new transport sites. The converse, i.e., the down-regulation of SRm upon bile salt deprivation, has not been demonstrated. We examined the effects of bile salt depletion for 24 h and 48 h on taurocholate SRm and bromsulphalein (BSP) SRm, and on [14C]taurocholate binding to isolated liver surface membranes in unrestrained external biliary fistula rats. Taurocholate SRm was significantly decreased by 35% and 51% in 24-h-depleted and 48-h-depleted rats, respectively, compared with control, sham-operated rats. Maximal taurocholate concentration in bile was also significantly lower in the bile-salt-deprived rats. In contrast, BSP SRm was not significantly different between depleted animals and controls. Bile salt depletion for 24 h and 48 h did not significantly alter liver surface membrane protein recovery and membrance enzyme specific activity including Na+ + K+-ATPase. Specific[14C] taurocholate binding to liver surface membranes was significantly decreased by 25% in 24-h-depleted rats compared with control rats. In contrast to taurocholate SRm, bile salt depletion for 48 h did not result in further reduction of specific taurocholate binding sites. This study demonstrates that taurocholate SRm progressively decreased in 24-h- and 48-h-bile salt-depleted rats, this being consistent with adaptive down-regulation of hepatic bile salt transport. This effect is selective, since BSP SRm was unaltered. The depressed taurocholate SRm can be explained at least in part by decreased bile salt receptor density in liver surface membranes. It appears to be unrelated to either a reduction in membrane surface area (membrane protein recovery and enzyme activity were unchanged in bile salt-depleted rats) or altered Na+ electrochemical gradients (Na+ + K+-ATPase activity was not significantly different between bile salt-depleted and control rats).
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    ADAPTIVE-CHANGES OF HEPATIC BILE-SALT TRANSPORT IN A MODEL OF REVERSIBLE INTERRUPTION OF THE ENTEROHEPATIC CIRCULATION IN THE RAT
    (1993) ACCATINO, L; HONO, J; KOENIG, C; PIZARRO, M; RODRIGUEZ, L
    The reversibility and time course of the adaptive changes in hepatic bile salt transport related to modifications of the bile salt enterohepatic circulation and bile salt pool size have not been previously studied. For this reason a model of reversible interruption of entero-hepatic circulation was characterized in unrestrained rats, which allowed the study of changes in hepatic bile salt transport following bile salt pool depletion and subsequent restoration by either the de novo synthesis of bile acids or i.v. administration of exogenous taurocholate. Rats subjected to biliary drainage for 24 h through a transduodenal common bile duct cannula, followed by removal of the cannula and restoration of the enterohepatic circulation were studied at 24, 48 and 72 h. Neither light and electron microscopy examination nor plasma biochemical parameters showed evidence of necrosis, fibrosis, cholestasis or inflammatory changes. Maximum taurocholate secretory rate decreased to 50% following 24-h bile salt depletion. After restoration of the enterohepatic circulation maximum taurocholate secretory rate progressively increased to normal values at 72 h, following the normalization of the bile salt pool size, which had a similar composition compared with controls. The same effect was obtained when the native bile salt pool was substituted with exogenous taurocholate. Thus, adaptive down-regulation of hepatic bile salt transport capacity is a reversible process, related to restoration of entero-hepatic circulation and normalization of bile salt pool size.