The Mel(1a) melatonin receptor is coupled to parallel signal transduction pathways
The Mel(1a) melatonin receptor is coupled to parallel signal transduction pathways
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DOI：
10.1210/en.138.1.397
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发表时间：
1997-01-01
期刊：
影响因子：
4.8
通讯作者：
Reppert, SM
中科院分区：
文献类型：
--
作者：
Godson, C;Reppert, SM
最近克隆的一个家庭的高亲和力褪黑激素受体为我们提供了一个独特的机会，以确定这些受体所使用的信号转导途径。我们通过在NIH 3T3细胞中稳定表达受体互补DNA来研究通过人Mel（1a）受体亚型的信号传导。我们的数据表明，人Mel（1a）受体与百日咳毒素敏感性G蛋白抑制毛喉素刺激的cAMP积累有关。尽管单独的褪黑激素对磷酸肌醇水解没有影响，但它增强了PGF（2 α）刺激对磷脂酶C活化的影响。褪黑激素增强PGF（2 α）和离子霉素刺激的花生四烯酸释放。褪黑激素对花生四烯酸释放的影响对蛋白激酶C的抑制敏感。它们独立于褪黑激素对cAMP的影响，并且似乎不涉及丝裂原活化蛋白激酶的活化。褪黑激素对磷脂酰肌醇水解和花生四烯酸释放的影响对百日咳毒素处理敏感。因此，我们表明，褪黑激素信号转导的平行途径，包括腺苷酸环化酶的抑制和增强磷脂酶的激活。
The recent cloning of a family of high affinity melatonin receptors has provided us with a unique opportunity to define the signal transduction pathways used by these receptors. We have studied signaling through the human Mel(1a) receptor subtype by stable expression of receptor complementary DNA in NIH 3T3 cells. Our data indicate that the human Mel(1a) receptor is coupled to inhibition of forskolin-stimulated cAMP accumulation by a pertussis toxin-sensitive G protein. Although melatonin alone is without effect on phosphoinositide hydrolysis, it potentiates the effects of PGF(2 alpha) stimulation on phospholipase C activation. Melatonin potentiates arachidonate release stimulated by PGF(2 alpha) and by ionomycin. The effects of melatonin on arachidonate release are sensitive to inhibition of protein kinase C. They are independent of the effects of melatonin on cAMP and do not appear to involve activation of mitogen-activated protein kinase. The effects of melatonin on both phosphoinositide hydrolysis and arachidonate release are sensitive to pertussis toxin treatment. Thus, we show that the melatonin signal is transduced by parallel pathways involving inhibition of adenylyl cyclase and potentiation of phospholipase activation.