2ND-MESSENGER GENERATION IN PC12-CELLS - INTERACTIONS BETWEEN CYCLIC-AMP AND CA-2+-SIGNALS
2ND-MESSENGER GENERATION IN PC12-CELLS - INTERACTIONS BETWEEN CYCLIC-AMP AND CA-2+-SIGNALS
复制标题
DOI：
10.1042/bj2550753
复制
发表时间：
1988-11-01
影响因子：
4.1
通讯作者：
MELDOLESI, J
中科院分区：
文献类型：
--
作者：
GATTI, G;MADEDDU, L;MELDOLESI, J
在暴露于各种处理的完整PC12嗜铬细胞瘤细胞中，研究了环AMP浓度的变化。N-（l -2-苯异丙基）腺苷（腺苷受体的激活剂）引起了显著的增加，而通过选择性毒蕈碱受体阻滞剂哌嗪平抑制的毒蕈碱受体，仅在高浓度（Ki 450 nM）下引起了减少（即使在磷酸二酯酶阻断后也观察到）。可乐定和。α也能引起环AMP的降低。2-adrenergic-receptor受体激动剂。都是。百日咳毒素预处理能抑制2-肾上腺素能和毒蕈碱的抑制，而12- o -十四烷酚13-醋酸酯对2-肾上腺素能和毒蕈碱的抑制不受影响。后一种药物引起静息环AMP浓度的降低，以及腺苷受体激活引起的增加的增强。除可乐定外，所有这些治疗方法都被发现对生长中的PC12细胞有效，并且在神经生长因子（NGF）长时间治疗后停止生长并获得神经元样表型的细胞有效，尽管程度较小。既不是福斯克林（腺苷酸环化酶的直接激活剂）也不是腺苷和α的激活。-肾上腺素能受体能够改变PC12细胞静息时胞浆内Ca2+浓度[Ca2+]i。同样，K+诱导的[Ca2+]i瞬态在这些处理后没有变化，而碳二醇通过激活对哌嗪高度敏感的毒蕈碱受体诱导的瞬态被福斯克林适度增强（在较小程度上，被腺苷类似物增强），并被可乐定减弱。这些结果进一步详细表征了PC12细胞中受体激活诱导的胞内信号的频谱和相互关系，也作为ngf诱导分化的功能。
Changes in cyclic AMP concentrations were studied in intact PC12 pheochromocytoma cells exposed to a variety of treatments. A marked increase was triggered by N-(L-2-phenylisopropyl)adenosine, the ativator of an adenosine receptor, whereas a decrease (observed even after phosphodiesterase blockade) was induced by carbachol, working through a muscarinic receptor inhibited by the selective muscarinic blocker pirenzepine, only at high concentration (Ki 450 nM). A decrease in cyclic AMP was also induced by clonidine, an .alpha.2-adrenergic-receptor agonist. Both the .alpha.2-adrenergic and the muscarinic inhibitions were prevented by pretreatment of the cells with pertussis toxin, and were unaffected by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate. The latter drug caused a decrease in the resting cyclic AMP concentrations, and a potentiation of the increase induced by adenosine-receptor activation. Except for clonidine, all these treatments were found to be effective in both growing PC12 cells and, although to a smaller degree, in cells that had stopped growing and had acquired a neuron-like phenotype after prolonged treatment with nerve growth factor (NGF). Neither forskolin (a direct activator of adenylate cyclase) nor the activation of adenosine and .alpha.-adrenergic receptors was able to modify the resting cytosolic Ca2+ concentration [Ca2+]i in PC12 cells. Likewise, the K+-induced [Ca2+]i transients were unchanged after these treatments, whereas the transients induced by carbachol through the activation of a muscarinic receptor highly sensitive to pirenzepine were moderately potentiated by forskolin (and, to a lesser degree, by the adenosine analogue) and attenuated by clonidine. These results characterize in further detail the spectrum and the mutual interrelationships of the intracellular signals induced by receptor activation in PC12 cells, also as a function of the NGF-induced differentiation.