Ishikawa S, Kusaka I, Higashiyama M, Nagasaka S, Saito T, Honda K, Saito T
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Kidney Int. 1996 Nov;50(5):1506-14. doi: 10.1038/ki.1996.465.
The present study was undertaken to determine whether low density lipoprotein (LDL) modulates the cellular action of arginine vasopressin (AVP) in cultured glomerular mesangial cells of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The AVP-induced cellular signal transduction, including inositol 1,4,5-trisphosphate (IP3) production, fura-2 intracellular calcium measurements and cellular alkalinization, was significantly greater in cells of SHR than those of WKY. This is based on an increase in AVP V1 receptor number in cells of the SHR. Also, the AVP activation of mitogen-activated protein (MAP) kinase and [3H]thymidine incorporation was significantly exaggerated in cells of SHR compared with those of WKY. LDL at a concentration of 10 micrograms/ml augmented the cellular signaling and proliferative action of AVP in cells of WKY, but not in those of SHR. Since [3H]AVP receptor binding was not affected by the LDL pretreatment, LDL modulates the signal transduction between a location distal to the AVP receptors and proximal from the production of IP3 and diacylglycerol. These results indicate that an increase in AVP receptor capacity has a profound effect on the AVP-induced cellular signaling and proliferation, and that LDL has a slight alteration on the action of AVP in glomerular mesangial cells of SHR.
本研究旨在确定低密度脂蛋白（LDL）是否调节自发性高血压大鼠（SHR）和正常血压Wistar-Kyoto大鼠（WKY）培养的肾小球系膜细胞中精氨酸加压素（AVP）的细胞作用。AVP诱导的细胞信号转导，包括肌醇1,4,5-三磷酸（IP3）产生、fura-2细胞内钙测量和细胞碱化，在SHR细胞中比WKY细胞中显著更强。这是基于SHR细胞中AVP V1受体数量的增加。此外，与WKY细胞相比，SHR细胞中丝裂原活化蛋白（MAP）激酶的AVP激活和[3H]胸苷掺入显著增强。浓度为10微克/毫升的LDL增强了WKY细胞中AVP的细胞信号转导和增殖作用，但对SHR细胞没有作用。由于[3H]AVP受体结合不受LDL预处理的影响，LDL调节AVP受体远端至IP3和二酰基甘油产生近端之间的信号转导。这些结果表明，AVP受体能力的增加对AVP诱导的细胞信号转导和增殖有深远影响，并且LDL对SHR肾小球系膜细胞中AVP的作用有轻微改变。
