Ursodeoxycholate-induced changes in hepatic Na+-H+ exchange and biliary HCO3- excretion.
Ursodeoxycholate-induced changes in hepatic Na+-H+ exchange and biliary HCO3- excretion.
复制标题
熊去氧胆酸诱导肝脏 Na -H 交换和胆汁 HCO3- 排泄的变化。
DOI：
10.1152/ajpgi.1989.257.3.g371
复制
发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Atkinson,JM
中科院分区：
文献类型：
--
作者：
Anwer,MS;Hondalus,MK;Atkinson,JM
熊去氧胆酸盐（UDC）诱导的富HCO 3胆汁分泌可能是由于激活了窦状Na+-H+交换，随后通过小管Cl- -HCO 3-交换增加了细胞内pH（pHi）和HCO 3-排泄。为了验证这一假设，我们研究了UDC和牛磺熊去氧胆酸盐（TUDC）对净H+流出灌注大鼠肝脏和pHi在离体肝细胞中存在和不存在阿米洛利的影响。阿米洛利可抑制UDC诱导的胆汁HCO 3-浓度和排泄增加。然而，这些增加与H+外排和pHi的初始下降以及随后逐渐恢复至基线在时间上相关。H+流出的初始下降与UDC的快速摄取相关。阿米洛利仅抑制H+流出和pHi的恢复期。TUDC增加阿米洛利敏感的H+流出，而不影响胆汁[HCO 3-]和降低pHi的存在，但不存在阿米洛利。阿米洛利减少TUDC诱导的胆汁分泌和HCO 3-排泄最有可能通过减少TUDC排泄。TUDC降低胆汁[Cl-]和增加肝脏O2摄取比UDC。我们得出结论，质子化形式的UDC的快速流入最初降低了pHi和净H+流出。恢复阶段是由于Na+-H+交换被降低的pHi和可能被UDC激活以及增加的细胞呼吸。TUDC间接刺激Na+-H+交换最有可能通过增加细胞呼吸。在净H+流出和pHi均低于对照值时观察到的UDC诱导的富HCO 3胆汁分泌不太可能是由于Na+-H+交换的直接激活。
Ursodeoxycholate (UDC)-induced HCO3- -rich choleresis may be due to activation of sinusoidal Na+-H+ exchange followed by an increase in intracellular pH (pHi) and HCO3- excretion via canalicular Cl- -HCO3- exchange. To test this hypothesis, we studied the effect of UDC and tauroursodeoxycholate (TUDC) on net H+ efflux from perfused rat livers and pHi in isolated hepatocytes in the presence and absence of amiloride. UDC-induced increases in biliary HCO3- concentration and excretion were inhibited by amiloride. However, these increases were temporally associated with an initial decline in H+ efflux and pHi followed by a gradual recovery toward base line. The initial decline in H+ efflux was associated with a rapid uptake of UDC. Amiloride inhibited only the recovery phases of H+ efflux and pHi. TUDC increased amiloride-sensitive H+ efflux without affecting biliary [HCO3-] and decreased pHi in the presence but not in the absence of amiloride. Amiloride decreased TUDC-induced choleresis and HCO3- excretion most likely by decreasing TUDC excretion. TUDC decreased biliary [Cl-] and increased hepatic O2 uptake more than UDC. We conclude that a rapid influx of UDC in the protonated form decreases pHi and net H+ efflux initially. The recovery phase is due to Na+-H+ exchange activated by decreased pHi and possibly by UDC and increased cellular respiration. TUDC indirectly stimulates Na+-H+ exchange most likely by increasing cellular respiration. UDC-induced HCO3- -rich choleresis, which is observed at a time when both net H+ efflux and pHi are less than control values, is unlikely to be due to a direct activation of Na+-H+ exchange.