Godson C, Reppert S M
Laboratory of Developmental Chronobiology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Endocrinology. 1997 Jan;138(1):397-404. doi: 10.1210/endo.138.1.4824.
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 Mel1a receptor subtype by stable expression of receptor complementary DNA in NIH 3T3 cells. Our data indicate that the human Mel1a 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 PGF2 alpha stimulation on phospholipase C activation. Melatonin potentiates arachidonate release stimulated by PGF2 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.
最近克隆出的一类高亲和力褪黑素受体，为我们界定这些受体所采用的信号转导途径提供了独特的契机。我们通过在NIH 3T3细胞中稳定表达受体互补DNA，研究了人类Mel1a受体亚型的信号传导。我们的数据表明，人类Mel1a受体通过一种对百日咳毒素敏感的G蛋白与抑制福斯高林刺激的环磷酸腺苷（cAMP）积累相偶联。虽然单独的褪黑素对磷酸肌醇水解没有影响，但它能增强前列腺素F2α（PGF2α）刺激对磷脂酶C激活的作用。褪黑素能增强PGF2α和离子霉素刺激的花生四烯酸释放。褪黑素对花生四烯酸释放的作用对蛋白激酶C的抑制敏感。它们独立于褪黑素对cAMP的作用，并且似乎不涉及丝裂原活化蛋白激酶的激活。褪黑素对磷酸肌醇水解和花生四烯酸释放的作用对百日咳毒素处理敏感。因此，我们表明褪黑素信号是通过涉及抑制腺苷酸环化酶和增强磷脂酶激活的平行途径转导的。
