Durieu-Trautmann O, Couraud P O, Foignant-Chaverot N, Strosberg A D
Laboratoire d'Immuno-Pharmacologie Moléculaire, CNRS UPR 0415, Université Paris VII, France.
Neurosci Lett. 1991 Oct 14;131(2):175-8. doi: 10.1016/0304-3940(91)90607-u.
The density of endothelin-1 (ET-1) receptors on rat astrocytoma C6 cells is down-regulated by activation of protein kinase C (PKC). We have investigated whether intracellular accumulation of cyclic adenosine monophosphate (cAMP) may also modulate surface ET-1 receptor number. The density of ET-1 receptors was measured by binding of [125I]ET-1 on rat astrocytoma C6 intact cells exposed to catecholamines, dibutyryl-cAMP or forskolin. Prolonged exposure of the cells to the beta-adrenergic agonists, isoproterenol or noradrenaline, results in a time- and dose-dependent decrease in cell surface ET-1 receptor number. This decrease proceeds slowly: maximal down-regulation is obtained by 6-7 h and sustained for up to 24 h in the presence of 10 microM isoproterenol. Since this down-regulation is mimicked by dibutyryl-cAMP (4 microM) and by forskolin (10 microM), we conclude that ET-1 receptors are susceptible to down-regulation through a cAMP-dependent pathway.
蛋白激酶C（PKC）的激活可下调大鼠星形细胞瘤C6细胞上内皮素-1（ET-1）受体的密度。我们研究了细胞内环磷酸腺苷（cAMP）的积累是否也可调节ET-1受体的表面数量。通过[125I]ET-1与暴露于儿茶酚胺、二丁酰-cAMP或福斯可林的大鼠星形细胞瘤C6完整细胞结合来测量ET-1受体的密度。细胞长时间暴露于β-肾上腺素能激动剂异丙肾上腺素或去甲肾上腺素会导致细胞表面ET-1受体数量出现时间和剂量依赖性减少。这种减少进展缓慢：在10μM异丙肾上腺素存在的情况下，6-7小时可获得最大下调，并且可持续长达24小时。由于二丁酰-cAMP（4μM）和福斯可林（10μM）可模拟这种下调，我们得出结论，ET-1受体易通过cAMP依赖性途径发生下调。
