title: Role of cAMP/PKA pathway and T-type calcium channels in the mechanism of action of serotonin in human adrenocortical cells.
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-HT4). The aim of the present study was to investigate the transduction mechanisms associated with activation of 5-HT4receptors in human adrenocortical cells. Our results show that 5-HT4receptors are present in the outer adrenal cortex, both in glomerulosa and fasciculata zonae. In the zona glomerulosa. 5-HT4receptor was detected both in immunopositive and immunonegative cells for 11β-hydroxylase, an enzyme involved in cortisol synthesis. The data demonstrate that 5-HT4receptors 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.
authors.affiliation: Normandie Univ, UNIROUEN, INSERM, DC2N, 76000, Rouen, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Louiset
authors.affiliation: Normandie Univ, UNIROUEN, INSERM, DC2N, 76000, Rouen, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Duparc
authors.affiliation: Unit of Toxicology, University Center of Legal Medicine, CH-1211 Geneva 4, Switzerland.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lenglet
authors.affiliation: Endocrine Section, Department of Medicine, G.V. (Sonny) Montgomery VA Medical Center, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Celso E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.affiliation: Normandie Univ, UNIROUEN, INSERM, DC2N, 76000, Rouen, France; Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital of Rouen, Rouen, France. Electronic address: herve.lefebvre@chu-rouen.fr.
authors.forename: Hervé
authors.initials: H
authors.lastname: Lefebvre
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology*; D002118:Calcium / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism
chemical_list: D020747:Calcium Channels, T-Type; D011985:Receptors, Serotonin; D012701:Serotonin; D000242:Cyclic AMP; D013252:Steroid 11-beta-Hydroxylase; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium; D006854:Hydrocortisone
keywords: 5-HT; Adrenocortical cells; Calcium current; Cortisol; Protein kinase A; cAMP