首页> 外文期刊>European Journal of Pharmacology: An International Journal >Desensitization of angiotensin-stimulated inositol phosphate accumulation in human vascular smooth muscle cells.
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Desensitization of angiotensin-stimulated inositol phosphate accumulation in human vascular smooth muscle cells.

机译:血管紧张素刺激的肌醇磷酸酯在人血管平滑肌细胞中的脱敏。

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摘要

The effect of angiotensin II treatment on desensitization of phospholipase C (PLC)-mediated inositol phosphate accumulation has not been quantitated in human aortic vascular smooth muscle (HVSM) cells. We determined the angiotensin II pretreatment dose dependency and time course for desensitization of PLC activation in HVSM cells and the effect of protein kinase C (PKC) activators on angiotensin II-mediated inositol phosphate accumulation. Our results with PKC activators and direct G protein stimulators suggest that PKC activation may play a negative feedback role in desensitization of angiotensin II-activated signaling in HVSM cells by modifying the Gq transducer, PLC-beta effector, or related proteins in the signaling pathway. However, neither angiotensin II nor PKC activator affected basal phosphorylation levels of PLC-beta1 or PLC-beta3 in HVSM cells; PLC-beta isoenzymes were shown to be phosphorylated in unstimulated cells independent of PKC inhibition. We suggest that desensitization of G protein-stimulated inositol phosphate accumulation in HVSM differs from other cell types in which phosphorylation of PLC-beta isoenzymes accompanies desensitization.
机译:在人类主动脉血管平滑肌(HVSM)细胞中,尚未量化血管紧张素II治疗对磷脂酶C(PLC)介导的肌醇磷酸积累的脱敏作用。我们确定了血管紧张素II预处理剂量依赖性和HVSM细胞中PLC激活脱敏的时间过程以及蛋白激酶C(PKC)活化剂对血管紧张素II介导的肌醇磷酸酯积累的影响。我们对PKC激活剂和直接G蛋白刺激剂的研究结果表明,PKC激活可能通过修饰Gq换能器,PLC-β效应子或信号传导途径中的相关蛋白,在HVSM细胞中血管紧张素II激活的信号减敏中发挥负反馈作用。然而,血管紧张素II和PKC激活剂均未影响HVSM细胞中PLC-beta1或PLC-beta3的基础磷酸化水平。已显示PLC-beta同工酶在不受刺激的细胞中被磷酸化,而与PKC抑制作用无关。我们建议HVSM中G蛋白刺激的肌醇磷酸积累的脱敏不同于其他细胞类型,其中PLC-β同工酶的磷酸化伴随脱敏。

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