Involvement of T-type calcium channels in the mechanism of action of 5-HT in rat glomerulosa cells: A novel signaling pathway for the 5-HT7 receptor

被引：12

作者：

Lenglet, S ^{[1
]}

Louiset, E ^{[1
]}

Delarue, C ^{[1
]}

Vaudry, H ^{[1
]}

Contesse, V ^{[1
]}

机构：

[1] Univ Rouen, CNRS,INSERM U413, Lab Cellular & Mol Neuroendocrinol, European Inst Peptide Res IFRMP 23, F-76821 Mont St Aignan, France

来源：

ENDOCRINE RESEARCH | 2002年 / 28卷 / 04期

关键词：

D O I：

10.1081/ERC-120016981

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We have previously demonstrated that, in rat, the stimulatory effect of 5-HT on aldosterone secretion is mediated through a 5-HT7 receptor subtype. The aim of the present study was to characterize the transduction mechanisms associated with activation of native 5-HT7 receptors. 5-HT induced a dose-dependent increase in cAMP production in rat glomerulosa cells. Pretreatment of cells with the adenylyl cyclase (AC) inhibitor SQ 22536 or the protein kinase A (PKA) inhibitor H-89 markedly attenuated the effect of 5-HT on aldosterone secretion. Administration of 5-HT in the vicinity of glomerulosa cells induced a robust increase in cytosolic calcium concentration ([Ca2+](i)) and this effect was abrogated by the T-type calcium channel blocker mibefradil. Patch-clamp studies confirmed that 5-HT activated a T-type calcium current. H-89 attenuated both the [Ca2+](i) response and the activation of T-type calcium current induced by 5-HT. Reduction of extracellular calcium concentration in the medium or administration of tnibefradil caused a marked reduction of the maximum effect (E-max) of 5-HT on aldosterone secretion. These data demonstrate that activation of native 5-HT7 receptors stimulates cAMP formation, which in turn provokes calcium influx through T-type

引用

页码：651 / 655

页数：5

共 5 条

[1] Pharmacological and molecular characterization of 5-hydroxytryptamine7 receptors in the rat adrenal gland [J].