Role of signal transduction systems in neurotensin receptor down-regulation induced by agonist in murine neuroblastoma clone N1E-115 cells.
Role of signal transduction systems in neurotensin receptor down-regulation induced by agonist in murine neuroblastoma clone N1E-115 cells.
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发表时间：
1993-10
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通讯作者：
M. Yamada;M. Yamada;E. Richelson
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作者：
M. Yamada;M. Yamada;E. Richelson
小鼠神经母细胞瘤克隆N1 E-115细胞具有神经降压素（NT）受体，其与导致聚磷酸肌醇（PI）水解和环GMP合成的信号转导系统偶联。以前，我们已经证明了在N1 E-115细胞中NT受体下调的过程涉及可回收受体的细胞内螯合，随后是受体降解，导致真正的下调。在这项研究中，激动剂诱导的NT受体在N1 E-115细胞中的隔离被氨基类固醇1-（6-（[17 β-3-甲氧基雌甾-1，3，5（10）-三烯-17-基]氨基）己基）-1H-吡咯-2，5-二烷（U-73122）抑制。由NT或氟化钠引起的Pl水解，其刺激GTP结合蛋白，也被U-73122抑制，而由钙离子载体、离子霉素或A23187引起的Pl水解没有明显影响。这些数据表明，U-73122影响的过程是远端的细胞表面受体，但不涉及的网站，只是接近PI水解或环GMP合成。这表明，U-73122可能影响GTP结合蛋白和NT受体的偶联。我们的结论是，GTP结合蛋白在激动剂诱导的NT受体下调N1 E-115细胞的机制中发挥重要作用。这些结果可能表明，GTP结合蛋白也发挥了作用，在中枢神经系统在体内的这种受体的内化机制。
Murine neuroblastoma clone N1E-115 cells possess neurotensin (NT) receptors, which are coupled to signal transduction systems resulting in polyphosphoinositide (Pl) hydrolysis and cyclic GMP synthesis. Previously, we have demonstrated that the process of down-regulation of NT receptors in N1E-115 cells involves intracellular sequestration of recyclable receptors followed by receptor degradation, causing true down-regulation. In this study, agonist-induced sequestration of NT receptors in N1E-115 cells was inhibited by an aminosteroid, 1-(6-([17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino)hexyl)-1H-pyrrole- 2,5-diane (U-73122). Pl hydrolysis elicited by NT or sodium fluoride, which stimulates GTP binding proteins, was also inhibited by U-73122, whereas Pl hydrolysis elicited by calcium ionophores, ionomycin or A23187, was not apparently affected. These data suggest that U-73122 affects a process that is distal to the cell surface receptor but not involving the sites just proximal to Pl hydrolysis or cyclic GMP synthesis. It is suggested that U-73122 may affect the coupling of GTP binding proteins and the NT receptor. We conclude that GTP binding proteins play an important role in the mechanism of agonist-induced down-regulation of NT receptors in N1E-115 cells. These results may indicate that GTP binding proteins also play a role in the mechanism of internalization of this receptor in the central nervous system in vivo.