Browsing by Author "ICARTE, MA"

Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    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).
  • Thumbnail Image
    Item
    ADAPTIVE REGULATION OF HEPATIC BILE-SALT TRANSPORT - EFFECTS OF ALLOXAN DIABETES IN THE RAT
    (W B SAUNDERS CO, 1991) ICARTE, MA; PIZARRO, M; ACCATINO, L
    The hepatic transport of bile salts appears to be adaptively regulated by changes in the bile salt pool size and in the flux of bile salt through the liver. The maximum secretory rate of taurocholate increases or decreases when the bile salt pool size is modified by either oral feeding of cholate or taurocholate (up-regulation) or prolonged bile salt depletion through a biliary fistula (down-regulation), respectively. It is not known whether adaptive regulation of hepatic bile salt transport operates under conditions in which the bile salt pool size is modified by endogenous changes in bile acid metabolism. Because experimental diabetes mellitus is associated with alterations in the synthesis of bile acids and total bile salt pool size and composition in the rat, we examined the effects of diabetes mellitus induced by alloxan (5 mg/100 gm body weight, intravenously) and insulin treatment on hepatic bile salt transport and relate the changes to bile salt pool size variations. At 3 days after alloxan injection (DIAB-3 group) both taurocholate maximum secretory rate and pool size were significantly decreased, whereas they were restored to normal values after 6 days of diabetes (DIAB-6 group). Insulinopenic diabetes for 14 days (DIAB-14 group) and for 24 days (DIAB-24 group) resulted in a marked increase of basal bile salt secretory rate (secondary to an increased contribution of cholate conjugates) and an enhanced taurocholate maximum secretory rate compared with control rates (147% and 188% increase, respectively) and with a group (PHARM-control) that received alloxan but did not develop detectable glycosuria (224% and 286% increase, respectively). In contrast, sulfobromophthalein maximum secretory rate was not significantly modified in 14-day diabetic rats compared with control rats. In addition, diabetic rats demonstrated a significant reduction of the bile salt-independent fraction of bile flow. Insulin treatment (3 units/100 gm body wt/day) in diabetic rats from day 0 (alloxan injection) to day 14 (INS-14 group) and from day 14 to day 24 after alloxan administration (INS-24 group) normalized basal bile salt secretion, taurocholate maximum secretory rate and the bile salt-independent fraction of bile flow. Bile salt pool size was significantly greater in DIAB-14 and DIAB-24 groups than in the control group (172% and 216% greater, respectively) and the PHARM-control group (246% and 309% greater, respectively). Insulin treatment prevented, in the INS-14 group, and reversed, in the INS-24 group, the increase of bile salt pool. Cholestyramine administration (5% wt/wt in the diet) to diabetic rats from day 0 (alloxan injection) to day 14 (CHOL-14 group) and from day 14 to day 24 after alloxan administration (CHOL-24 group) prevented and reversed, respectively, bile salt pool and taurocholate maximum secretory rate increase without modifying the hyperglycemia.