Eistetter H R, Mills A, Brewster R, Alouani S, Rambosson C, Kawashima E
Department of Cell Biology, Glaxo Institute for Molecular Biology S.A., Plan-les-Ouates, Switzerland.
Glia. 1992;6(2):89-95. doi: 10.1002/glia.440060203.
The neurokinin-1 (NK-1, substance P) receptor belongs to the class of seven transmembrane domain (7-TM) receptors that interact with cellular effector systems via guanine nucleotide binding regulatory proteins (G-proteins). In this study, coupling mechanisms of functional NK-1 receptors endogenously expressed in a human astrocytoma cell line (U373MG) were analyzed. Stimulation with substance P (SP) resulted in 1) a rapid increase in inositol 1,4,5-trisphosphate (IP3) synthesis; 2) a rise in cytosolic free calcium concentration ([Ca2+]i); 3) induction of immediate early gene transcription as monitored by c-fos and c-jun expression; and 4) a significant increase in de novo DNA synthesis. Thus, the functional responses induced by stimulation of NK-1 receptors on U373MG strongly correlate with those observed after treatment of primary astrocytes with SP and make U373MG cells a useful in vitro model system for the analysis of NK-1 receptor function on astrocytes in vivo.
神经激肽-1（NK-1，P物质）受体属于七跨膜结构域（7-TM）受体家族，该家族通过鸟嘌呤核苷酸结合调节蛋白（G蛋白）与细胞效应系统相互作用。在本研究中，分析了人星形细胞瘤细胞系（U373MG）中内源性表达的功能性NK-1受体的偶联机制。用P物质（SP）刺激导致：1）肌醇1,4,5-三磷酸（IP3）合成迅速增加；2）胞质游离钙浓度（[Ca2+]i）升高；3）通过c-fos和c-jun表达监测到立即早期基因转录的诱导；4）从头DNA合成显著增加。因此，U373MG上NK-1受体刺激诱导的功能反应与原代星形胶质细胞用SP处理后观察到的反应密切相关，使U373MG细胞成为分析体内星形胶质细胞上NK-1受体功能的有用体外模型系统。
