环磷酸腺苷/蛋白激酶A信号通路及T型钙通道在5-羟色胺对人肾上腺皮质细胞作用机制中的作用
Role of cAMP/PKA pathway and T-type calcium channels in the mechanism of action of serotonin in human adrenocortical cells.
作者信息
Louiset Estelle, Duparc Céline, Lenglet Sébastien, Gomez-Sanchez Celso E, Lefebvre Hervé
机构信息
Normandie Univ, UNIROUEN, INSERM, DC2N, 76000, Rouen, France.
Unit of Toxicology, University Center of Legal Medicine, CH-1211 Geneva 4, Switzerland.
出版信息
Mol Cell Endocrinol. 2017 Feb 5;441:99-107. doi: 10.1016/j.mce.2016.10.008. Epub 2016 Oct 12.
Abstract
In human adrenal, serotonin (5-HT), produced by mast cells located in zona glomerulosa, stimulates production of corticosteroids through a paracrine mechanism involving the 5-HT receptor type 4 (5-HT). The aim of the present study was to investigate the transduction mechanisms associated with activation of 5-HT receptors in human adrenocortical cells. Our results show that 5-HT receptors are present in the outer adrenal cortex, both in glomerulosa and fasciculata zonae. In the zona glomerulosa. 5-HT receptor was detected both in immunopositive and immunonegative cells for 11β-hydroxylase, an enzyme involved in cortisol synthesis. The data demonstrate that 5-HT receptors are positively coupled to adenylyl cyclases and cAMP-dependent protein kinases (PKA). The activation of the cAMP-PKA pathway is associated with calcium influx through T-type calcium channels. Both the adenylyl cyclase/PKA pathway and the calcium influx are involved in 5-HT-induced cortisol secretion.
摘要
在人肾上腺中，位于球状带的肥大细胞产生的血清素（5-羟色胺，5-HT）通过涉及4型5-HT受体（5-HT）的旁分泌机制刺激皮质类固醇的产生。本研究的目的是研究与人肾上腺皮质细胞中5-HT受体激活相关的转导机制。我们的结果表明，5-HT受体存在于肾上腺皮质外层，在球状带和束状带中均有。在球状带，在11β-羟化酶（一种参与皮质醇合成的酶）免疫阳性和免疫阴性细胞中均检测到5-HT受体。数据表明，5-HT受体与腺苷酸环化酶和cAMP依赖性蛋白激酶（PKA）正偶联。cAMP-PKA途径的激活与通过T型钙通道的钙内流有关。腺苷酸环化酶/PKA途径和钙内流均参与5-HT诱导的皮质醇分泌。
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