Raible D W, McMorris F A
Wistar Institute, Philadelphia, PA 19104.
J Neurosci Res. 1990 Sep;27(1):43-6. doi: 10.1002/jnr.490270107.
Oligodendrocyte differentiation is accelerated by analogs of cyclic AMP (cAMP), such as N6,2-'O-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP) or 8-bromo cAMP, in developing rat glial cell cultures (Raible and McMorris, 1989). However, it is not known whether the immature developing oligodendrocytes have G protein-coupled adenylate cyclase capable of generating cAMP, as would be required if development of the cells is normally regulated by endogenous cAMP. In the present study, we demonstrate that the diterpene forskolin, a potent activator of adenylate cyclase, or cholera toxin, which activates adenylate cyclase through G protein modification, can induce a precocious increase in oligodendrocyte number. When both forskolin and cholera toxin are added together, oligodendrocyte differentiation is induced to a level similar to that observed in response to cAMP analogs. These results establish for the first time that modulation of the endogenous cAMP regulatory system alters the schedule of oligodendrocyte differentiation.
在发育中的大鼠神经胶质细胞培养物中，环磷酸腺苷（cAMP）类似物，如N6,2'-O-二丁酰腺苷3',5'-环磷酸（dbcAMP）或8-溴环磷酸腺苷，可加速少突胶质细胞的分化（雷布尔和麦克莫里斯，1989年）。然而，尚不清楚未成熟的发育中的少突胶质细胞是否具有能够产生cAMP的G蛋白偶联腺苷酸环化酶，而如果细胞的发育正常受内源性cAMP调节，就需要这种酶。在本研究中，我们证明二萜类化合物福斯高林（一种有效的腺苷酸环化酶激活剂）或霍乱毒素（通过修饰G蛋白激活腺苷酸环化酶）可诱导少突胶质细胞数量过早增加。当福斯高林和霍乱毒素一起添加时，少突胶质细胞的分化被诱导到与对cAMP类似物反应时观察到的水平相似。这些结果首次证实内源性cAMP调节系统的调节会改变少突胶质细胞分化的进程。
