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

Autor:	Estelle Louiset, V. Contesse, Catherine Delarue, S. Lenglet, Hubert Vaudry
Rok vydání:	2002
Předmět:	Serotonin medicine.medical_specialty Patch-Clamp Techniques medicine.drug_class Calcium channel blocker In Vitro Techniques Adenylyl cyclase Calcium Channels T-Type chemistry.chemical_compound Cytosol Endocrinology Internal medicine Cyclic AMP medicine Animals Enzyme Inhibitors Protein kinase A Aldosterone Sulfonamides Mibefradil Dose-Response Relationship Drug Voltage-dependent calcium channel Chemistry Adenine T-type calcium channel General Medicine Calcium Channel Blockers Isoquinolines Cyclic AMP-Dependent Protein Kinases Rats Receptors Serotonin Adenylyl Cyclase Inhibitors Calcium Zona Glomerulosa Signal transduction Signal Transduction medicine.drug
Zdroj:	Endocrine Research. 28:651-655
ISSN:	1532-4206 0743-5800
Popis:	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 mibefradil caused a marked reduction of the maximum effect (Emax) 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 calcium channels. Both the activation of the AC/PKA pathway and the calcium influx are involved in 5-HT-induced aldosterone secretion.
Databáze:	OpenAIRE
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