Hormonal-dependent recruitment of Na+,K+-ATPase to the plasmalemma is mediated by PKC beta and modulated by [Na+]i.
Hormonal-dependent recruitment of Na+,K+-ATPase to the plasmalemma is mediated by PKC beta and modulated by [Na+]i.
复制标题
Na ,K -ATP 酶向质膜的激素依赖性募集由 PKC beta 介导并由 [Na ]i 调节。
DOI：
10.1038/sj.bjp.0704962
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发表时间：
2002
影响因子：
7.3
通讯作者：
Pedemonte,CarlosH
中科院分区：
文献类型：
--
作者：
Budu,ClaudiaE;Efendiev,Riad;Cinelli,AngelM;Bertorello,AlejandroM;Pedemonte,CarlosH
摘要1本研究表明，用8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）刺激近端小管细胞的激素受体，可诱导Na [Na +]，K [Na +]-ATP酶活性的增强，这是由于酶分子被募集到质膜上。2表达啮齿类野生型Na [Na +]，K [Na +]-ATP酶α亚基的细胞与表达α亚基S11 A-S18 A突变体的细胞具有相同的基础Na [Na +]，K [Na +]-ATP酶活性，但两种突变体对Na [Na +]，K [Na +]-ATP酶活性的刺激作用均完全消失。38-OH-DPAT处理OK细胞后，α亚基Ser-11和Ser-18残基发生PKC依赖性磷酸化，S11 A和S18 A突变体的酶活性测定表明，这两个残基对激动剂依赖性的Na [Na +]，K [Na +]-ATP酶活性的刺激是必需的。4.多巴胺和8-OH-DPAT同时作用于细胞时，在基础细胞内钠浓度（~ 19 mM）时，可观察到Na [Na +]，K [Na +]-ATP酶的激活，随着细胞内钠浓度从9 mM逐渐增加到19 mM，这种激活逐渐减弱，并成为明显的抑制。细胞内钠调节Na [Na +]，K [Na +]-ATP酶的激活或抑制。
Abstract 1 The present study demonstrates that stimulation of hormonal receptors of proximal tubule cells with the serotonin-agonist 8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT) induces an augmentation of Na [SUP+], K [SUP+]-ATPase activity that results from the recruitment of enzyme molecules to the plasmalemma. 2 Cells expressing the rodent wild-type Na [SUP+], K [SUP+]-ATPase α-subunit had the same basal Na [SUP+], K [SUP+]-ATPase activity as cells expressing the α-subunit S11A S18A mutants, but stimulation of Na [SUP+], K [SUP+]-ATPase activity was completely abolished in either mutant. 3 8-OH-DPAT treatment of OK cells led to PKC-dependent phosphorylation of the α-subunit Ser-11 and Ser-18 residues, and determination of enzyme activity with the S11A and S18A mutants indicated that both residues are essential for the agonist-dependent stimulation of Na [SUP+], K [SUP+]-ATPase activity. 4 When cells were treated with both dopamine and 8-OH-DPAT, and activation of Na [SUP+], K [SUP+]-ATPase was observed at basal intracellular sodium concentration (∼ 9 mM), and this activation was gradually reduced and became a significant inhibition as the concentration of intracellular sodium gradually increased from 9 to 19 mM. Thus, besides the antagonistic effects of dopamine and 8-OH-DPAT, intracellular sodium modulates whether an activation or an inhibition of Na [SUP+], K [SUP+]-ATPase is produced.