Relationship between phospholipase C activation and prostaglandin E2 and cyclic adenosine monophosphate production in rabbit tubular epithelial cells. Effects of angiotensin, bradykinin, and arginine vasopressin.

Relationship between phospholipase C activation and prostaglandin E2 and cyclic adenosine monophosphate production in rabbit tubular epithelial cells. Effects of angiotensin, bradykinin, and arginine vasopressin.
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兔肾小管上皮细胞磷脂酶 C 活化与前列腺素 E2 和环磷酸腺苷生成之间的关系。

DOI:
10.1172/jci113376
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发表时间:
1988
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Douglas,JG
Douglas,JG
中科院分区:
--
文献类型:
--
作者:
Welsh,C;Dubyak,G;Douglas,JG

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通过采用早期传代的兔肾上皮细胞在组织培养中,我们证明了血管紧张素II(AII)具有独特的信号转导机制。首先,与其在其他靶组织中的作用不同,需要微摩尔浓度的AII来诱导细胞溶质钙[Ca 2 +]i的小幅升高,这种作用不伴随肌醇磷酸(IP)的释放。相比之下,纳摩尔缓激肽(BK)通过激活磷脂酶C和释放IP动员[Ca 2 +]i。这些刺激的钙反应都没有表现出百日咳毒素(PTx)的敏感性。其次,10(-9)至10(-7)M的AII和BK通过远端细胞中PGE 2的产生间接刺激cAMP。AII-和BK-刺激的PGE 2释放是PTx抑制,提示存在GTP结合蛋白介导的反应。相比之下,精氨酸加压素不能引起[Ca 2 +]i的升高,但通过与刺激性GTP结合蛋白的直接偶联对远端细胞中的cAMP产生发挥其主要作用,如通过与霍乱毒素解偶联所证明的。PGE 2合成的调节似乎是通过磷脂酶A2而不是C来进行的,这三种肽都是如此。图片
By employing early-passaged rabbit kidney epithelial cells in tissue culture, we demonstrated that angiotensin II (AII) has unique mechanisms of signal transduction. First, unlike its action in other target tissues, micromolar concentrations of AII are required to induce small rises in cytosolic calcium, [Ca2+]i, an action which is not accompanied by the release of inositol phosphates (IP). In contrast, nanomolar bradykinin (BK) mobilizes [Ca2+]i through activation of phospholipase C and release of IP. Neither of these stimulated calcium responses exhibits pertussis toxin (PTx) sensitivity. Secondly, AII and BK at 10(-9) to 10(-7) M stimulate cAMP indirectly through PGE2 production in distal cells. AII- and BK-stimulated PGE2 release is PTx inhibitible, suggestive of the presence of a GTP binding protein mediating the response. By contrast, arginine vasopressin fails to elicit rises in [Ca2+]i but exerts its primary effect on cAMP production in distal cells via direct coupling to a stimulatory GTP binding protein, as evidenced by uncoupling with cholera toxin. Regulation of PGE2 synthesis appears to occur via phospholipase A2, not C, by all three peptides.Images
百日咳毒素可消除大鼠肾系膜细胞中血管紧张素 II 诱导的磷酸肌醇水解和前列腺素合成。
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