Mechanism of activation of the NA+/H+ exchanger by arginine vasopressin in hepatocytes

Mechanism of activation of the NA+/H+ exchanger by arginine vasopressin in hepatocytes
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精氨酸加压素激活肝细胞NA/H交换体的机制

DOI:
10.1002/hep.1840200531
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发表时间:
1994
期刊:
影响因子:
13.5
通讯作者:
M. Anwer
M. Anwer
中科院分区:
医学1区
文献类型:
--
作者:
M. Anwer

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精氨酸加压素已被证明通过钙/钙调蛋白依赖性过程激活肝细胞中的Na/H+交换器。在这项研究中,这种激活是否也涉及蛋白激酶C,并与细胞内pH值设定点的变化有关。分别用荧光探针BCECF和quin-2测量pHi和细胞内Ca++浓度的变化。细胞内pH恢复率根据丙酸钠负载的肝细胞内pH的时间依赖性变化计算。精氨酸加压素,佛波醇肉豆蔻酸酯乙酸酯和毒胡萝卜素刺激细胞内pH值的恢复,但没有增加基础细胞内pH值。精氨酸加压素和毒胡萝卜素,但不是佛波醇肉豆蔻酸酯乙酸酯,增加细胞内Ca++浓度。蛋白激酶C抑制剂staurosporine和calphostin C抑制精氨酸加压素和佛波酯myrivalacetate诱导的细胞内pH恢复,但不抑制毒胡萝卜素诱导的细胞内pH恢复。星形孢菌素和钙磷蛋白C均不影响精氨酸加压素和毒胡萝卜素诱导的细胞内Ca++浓度升高,也没有抑制剂影响基础细胞内pH恢复。精氨酸加压素,佛波酯myrivaline醋酸盐和毒胡萝卜素增加细胞内pH依赖性的细胞内pH恢复,而不影响细胞内pH设定值。这些结果表明,激活的Na+/H+交换精氨酸加压素介导的Ca++/钙调素和蛋白激酶C,可能是由于增强的相互作用的H+与交换器的内部修饰位点。(Hepatology 1994;20:1309-1317)。
Arginine vasopressin has been shown to activate the Na/H+ exchanger in hepatocytes by calcium/calmodulin‐dependent processes. Whether this activation also involves protein kinase C and is associated with changes in the intracellular pH setpoint was investigated in this study. Changes in pHi and intracellular Ca++ concentration were measured with the fluorescent probes BCECF and quin‐2, respectively. Intracellular pH recovery rate was calculated from timedependent changes in intracellular pH in hepatocytes acid‐loaded with sodium propionate. Arginine vasopressin, phorbol myristate acetate and thapsigargin stimulated intracellular pH recovery but did not increased basal intracellular pH. Arginine vasopressin and thapsigargin, but not phorbol myristol acetate, increased intracellular Ca++ concentration. The protein kinase C inhibitors staurosporine and calphostin C inhibited arginine vasopressin‐ and phorbol myristol acetate—induced, but not thapsigargin‐induced, intracellular pH recovery. Neither staurosporine nor calphostin C affected arginine vasopressin‐ and thapsigargin‐induced increases in intracellular Ca++ concentration, and no inhibitor affected basal intracellular pH recovery. Arginine vasopressin, phorbol myristol acetate and thapsigargin increased intracellular pH dependency of intracellular pH recovery without affecting intracellular pH setpoint. These results indicate that the activation of the Na+/H+ exchanger by arginine vasopressin is mediated both by Ca++/calmodulin and protein kinase C and may be due to enhanced interaction of H+ with the internal modifier site of the exchanger. (Hepatology 1994;20:1309–1317).
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DOI: --
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期刊: The Journal of biological chemistry
影响因子: --
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DOI: 10.1016/s0021-9258(19)50428-8
发表时间: 1992-05
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