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Pharmacological and Molecular Characterization of 5-Hydroxytryptamine 7 Receptors in the Rat Adrenal Gland

Abstract : Serotonin (5-hydroxytryptamine; 5-HT) is a potent stimulator of aldosterone secretion in the rat adrenal gland but the type of receptor involved in the mechanism of action of 5-HT remains unknown. The aim of the present study was to determine the pharmacological profile and to clone the receptor responsible for the corticotropic effect of 5-HT in rat glomerulosa cells. A series of 10 serotonergic receptor agonists and 12 receptor antagonists was used to characterize the receptor mediating the effect of 5-HT on aldosterone secretion from perifused rat adrenocortical slices. Correlation analysis between the potencies of the different compounds in our model and those previously reported for various recombinant 5-HT receptors showed that the rat adrenal 5-HT receptor exhibits the same pharmacological profile as the 5-HT(7) receptor transiently expressed in COS-7 cells (r = 0.82 for agonists, p <.05; r = 0.83 for antagonists, p <.01). Polymerase chain reaction with specific primers revealed the expression of 5-HT(7) receptor mRNA in the rat adrenal gland. Cloning of the polymerase chain reaction product confirmed that the amplified DNA corresponded to the 5-HT(7) receptor cDNA sequence. Western blot analysis showed the presence of a protein with an apparent molecular mass of 66 kDa in the adrenal cortex but not in the medulla. Taken together, these data demonstrate that the rat adrenal glomerulosa expresses functional 5-HT(7) receptors. Rat glomerulosa cells will thus provide a robust and sensitive bioassay for future studies on native 5-HT(7) receptors.
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Contributor : Isabelle Lihrmann Connect in order to contact the contributor
Submitted on : Friday, January 3, 2020 - 2:21:35 PM
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Vincent Contesse, Sebastien Lenglet, Luca Grumolato, Youssef Anouar, Isabelle Lihrmann, et al.. Pharmacological and Molecular Characterization of 5-Hydroxytryptamine 7 Receptors in the Rat Adrenal Gland. Molecular Pharmacology, American Society for Pharmacology and Experimental Therapeutics, 1999, 56 (3), pp.552-561. ⟨10.1124/mol.56.3.552⟩. ⟨hal-02427287⟩



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