Pastuszko A, Yee D K, Nelson D, Wilson D F
Department of Biochemistry and Biophysics, Medical School, University of Pennsylvania, Philadelphia 19104.
Cancer Biochem Biophys. 1988 Jul;10(1):67-76.
Three human neuroblastoma cell lines were shown to have markedly different contents of catecholamines and serotonin. Two of the cell lines (CHP-134 and IMR-5) have higher levels of dopamine and its metabolites, while CHP-404 cells have higher levels of serotonin and its metabolites. Each cell line responded to the addition of D,L-2-amino-5-phosphonovalerate, an agent which increases plasma membrane permeability to Ca2+ (Pastuszko and Wilson, 1988; with striking changes in the metabolism of the neurotransmitters. These changes were dependent on the extracellular calcium concentration and include activation of dopamine synthesis (tyrosine hydroxylase), increased levels of dihydroxyphenylacetic acid and increased formation of N-methylated dopamine derivatives. Catabolism of serotonin to 5-hydroxyindole acetic acid was inhibited while that to 5-hydroxytryptophol was stimulated. These data clearly identify several important sites for regulation of neurotransmitter metabolism by calcium. The mechanisms, direct or indirect, by which the enzyme activities are modulated by calcium remain to be established.
三种人类神经母细胞瘤细胞系显示出儿茶酚胺和血清素含量明显不同。其中两种细胞系(CHP - 134和IMR - 5)的多巴胺及其代谢产物水平较高,而CHP - 404细胞的血清素及其代谢产物水平较高。每个细胞系对添加D,L - 2 - 氨基 - 5 - 磷酸戊酸(一种增加质膜对Ca2 +通透性的试剂)(Pastuszko和Wilson,1988)都有反应,神经递质的代谢发生了显著变化。这些变化取决于细胞外钙浓度,包括多巴胺合成的激活(酪氨酸羟化酶)、二羟基苯乙酸水平的增加以及N - 甲基化多巴胺衍生物形成的增加。血清素分解为5 - 羟基吲哚乙酸受到抑制,而分解为5 - 羟基色醇则受到刺激。这些数据清楚地确定了钙调节神经递质代谢的几个重要位点。钙调节酶活性的直接或间接机制仍有待确定。