Vasopressin stimulates sodium transport in A6 cells via a phosphatidylinositide 3-kinase-dependent pathway.

Vasopressin stimulates sodium transport in A6 cells via a phosphatidylinositide 3-kinase-dependent pathway.
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加压素通过磷脂酰肌醇 3 激酶依赖性途径刺激 A6 细胞中的钠转运。

DOI:
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发表时间:
1999
期刊:
AJP - Renal Physiology
影响因子:
--
通讯作者:
John P. Johnson
John P. Johnson
中科院分区:
--
文献类型:
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作者:
R. Edinger;M. D. Rokaw;John P. Johnson

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磷脂酰肌醇 3-激酶 (PI3K) 磷酸化肌醇磷脂的肌醇环的 D-3 位并产生 3-磷酸化肌醇。这些新颖的第二信使被认为介导多种细胞信号传导功能。真菌代谢物渥曼青霉素与 PI3K 共价结合并选择性抑制其活性。使用这种特异性抑制剂检查了 PI3K 在基础和激素刺激的跨上皮钠转运中的作用。 50 nM 渥曼青霉素不影响 A6 细胞中的基础、醛固酮刺激或胰岛素刺激的转运。渥曼青霉素完全抑制加压素对这些细胞中转运的刺激。加压素刺激 A6 细胞中的 PI3K 活性。加压素对转运的刺激也可以被 5 μM LY-294002(第二种 PI3K 抑制剂)阻断。与渥曼青霉素预孵育一小时可阻断加压素对细胞中蛋白激酶 A 活性的刺激。对直接激活腺苷酸环化酶的外源 cAMP 和毛喉素的钠转运反应不受渥曼青霉素的影响。这些结果表明,渥曼青霉素在接近腺苷酸环化酶激活的位点抑制加压素对Na+转运的刺激。结果表明 PI3K 可能参与加压素受体激活。
The enzyme phosphatidylinositide 3-kinase (PI3K) phosphorylates the D-3 position of the inositol ring of inositol phospholipids and produces 3-phosphorylated inositides. These novel second messengers are thought to mediate diverse cellular signaling functions. The fungal metabolite wortmannin covalently binds to PI3K and selectively inhibits its activity. The role of PI3K in basal and hormone-stimulated transepithelial sodium transport was examined using this specific inhibitor. Wortmannin, 50 nM, did not affect basal, aldosterone-stimulated, or insulin-stimulated transport in A6 cells. Wortmannin completely inhibits vasopressin stimulation of transport in these cells. Vasopressin stimulates PI3K activity in A6 cells. Vasopressin stimulation of transport is also blocked by 5 μM LY-294002, a second inhibitor of PI3K. One-hour preincubation with wortmannin blocked vasopressin stimulation of protein kinase A activity in the cells. Sodium transport responses to exogenous cAMP and forskolin, which directly activates adenylate cyclase, were not affected by wortmannin. These results indicate that wortmannin inhibits vasopressin stimulation of Na+transport at a site proximal to activation of adenylate cyclase. The results suggest that PI3K may be involved in receptor activation by vasopressin.
G 蛋白激活抑制 A6 细胞中阿米洛利可阻断的高选择性钠通道。
DOI: 10.1152/ajpcell.1993.264.2.c352
发表时间: 1993
期刊: The American journal of physiology
影响因子: --
作者:
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DOI: --
发表时间: 1990
期刊: The Journal of biological chemistry
影响因子: --
作者:
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