Stimulation of inositol trisphosphate and diacylglycerol production in renal tubular cells by parathyroid hormone.

Stimulation of inositol trisphosphate and diacylglycerol production in renal tubular cells by parathyroid hormone.
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甲状旁腺激素刺激肾小管细胞产生肌醇三磷酸和二酰甘油。

DOI:
10.1172/jci112788
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发表时间:
1987
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Huskey,M
Huskey,M
中科院分区:
--
文献类型:
--
作者:
Hruska,KA;Moskowitz,D;Esbrit,P;Civitelli,R;Westbrook,S;Huskey,M

文献摘要

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甲状旁腺激素(PTH)对负鼠肾细胞系、原代培养的近端肾小管细胞和犬近端肾小管段的基底外膜产生三磷酸肌醇和二酰基甘油产生剂量依赖性。三磷酸肌醇产量的增加伴随着磷酸肌醇的少量增加,而二磷酸肌醇产量没有显著增加。与三磷酸肌醇和二酰基甘油的变化相关的是,磷脂酰肌醇4'5-二磷酸立即水解。影响磷脂水解后,刺激磷脂酰肌醇4′单磷酸和磷脂酰肌醇磷酸化。PTH在负鼠肾细胞中产生细胞质Ca2+的突然增加,持续约1分钟。三磷酸肌醇在皂素处理的负鼠肾脏和原代培养的近端小管细胞中瞬间增加细胞质Ca2+。环核苷酸不能模拟甲状旁腺素的作用。事实上,环状AMP似乎减少了肌醇三磷酸的产生。这些结果表明,甲状旁腺激素可能通过产生肌醇三磷酸和二酰基甘油来激活肾小管上皮细胞。图片
Parathyroid hormone (PTH) produced a dose-dependent immediate stimulation of inositol triphosphate and diacylglycerol production in the opossum kidney cell line, primary culture proximal tubular cells, and basolateral membranes from canine proximal tubular segments. The increase in inositol triphosphate production was accompanied by a minor increase in inositol phosphate and no significant increase in inositol bisphosphate production. Associated with the changes in inositol triphosphate and diacylglycerol, there was an immediate hydrolysis of phosphatidylinositol 4'5-bisphosphate. The effect on phospholipid hydrolysis was followed by stimulation of phosphorylation of phosphatidylinositol 4' monophosphate and phosphatidylinositol. PTH produced a sudden increase in cytoplasmic Ca2+ in opossum kidney cells that persisted for approximately 1 min. Inositol triphosphate transiently increased cytoplasmic Ca2+ in saponin-treated opossum kidney and primary culture proximal tubule cells. The effects of PTH were not mimicked by cyclic nucleotides. In fact, cyclic AMP appeared to diminish inositol triphosphate production. These results demonstrate that PTH may activate renal tubular epithelial cells by the production of inositol triphosphate and diacylglycerol.Images