Yu V C, Hochhaus G, Chang F H, Richards M L, Bourne H R, Sadée W
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143.
J Neurochem. 1988 Dec;51(6):1892-9. doi: 10.1111/j.1471-4159.1988.tb01174.x.
Neuroblastoma cells in culture contain low levels of cyclic AMP, a second messenger which plays a major role in neuronal maturation. In this study, human neuroblastoma cells, SK-N-SH-SY5Y, were induced to differentiate by treatment with either nerve growth factor (50 ng/ml), retinoic acid (10 microM), dibutyryl cyclic AMP (1 mM), or 12-O-tetradecanoylphorbol-13-acetate (0.1 microM), and the ability of several neurotransmitters or hormones to stimulate adenylyl cyclase was tested. Although all four differentiation factors caused morphological changes towards a neuronal phenotype, only retinoic acid dramatically enhanced cyclic AMP accumulation, specifically upon stimulation with prostaglandin E1 (PGE1). PGE2 was also active, but less potent, than PGE1, whereas the other cyclic AMP-stimulating agents tested were largely unaffected. Further, the rapid desensitization of the PGE1-cyclic AMP response observed in control cells after 20 min of PGE1 exposure did not occur in retinoic acid-treated cells, and the EC50 values for PGE1 were reduced from approximately 240 to 14 nM after retinoic acid treatment. The increased sensitivity to PGE was associated with an increase of high-affinity PGE1 binding sites, whereas the Gs coupling proteins and adenylyl cyclase were not measurably affected. A similar enhancement of the PGE1-cyclic AMP response by retinoic acid was also observed in two additional human neuroblastoma cell lines tested, Kelly and IMR-32, suggesting that up-regulation of the prostaglandin response by retinoic acid is common among neuroblastoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)
培养中的神经母细胞瘤细胞含有低水平的环磷酸腺苷（一种在神经元成熟过程中起主要作用的第二信使）。在本研究中，人神经母细胞瘤细胞SK-N-SH-SY5Y用神经生长因子（50 ng/ml）、视黄酸（10 μM）、二丁酰环磷酸腺苷（1 mM）或12-O-十四酰佛波醇-13-乙酸酯（0.1 μM）处理以诱导分化，并测试了几种神经递质或激素刺激腺苷酸环化酶的能力。尽管所有四种分化因子都引起了向神经元表型的形态变化，但只有视黄酸显著增强了环磷酸腺苷的积累，特别是在前列腺素E1（PGE1）刺激后。PGE2也有活性，但比PGE1的效力小，而测试的其他环磷酸腺苷刺激剂基本不受影响。此外，在视黄酸处理的细胞中，未观察到PGE1暴露20分钟后对照细胞中出现的PGE1-环磷酸腺苷反应的快速脱敏，视黄酸处理后PGE1的EC50值从约240 nM降至14 nM。对PGE敏感性的增加与高亲和力PGE1结合位点的增加有关，而Gs偶联蛋白和腺苷酸环化酶未受到明显影响。在另外两个测试的人神经母细胞瘤细胞系Kelly和IMR-32中也观察到视黄酸对PGE1-环磷酸腺苷反应的类似增强，这表明视黄酸对前列腺素反应的上调在神经母细胞瘤细胞中很常见。（摘要截短于250字）
