Role of cAMP/PKA pathway and T-type calcium channels in the mechanism of action of serotonin in human adrenocortical cells

•Serotonin (5-HT) is produced by mast cells located in zona glomerulosa of human adrenal.•5-HT receptor type 4 (5-HT4) is expressed by cortisol-producing cells positive for 11β-hydroxylase.•5-HT4 receptors are positively coupled to adenylyl cyclase (AC) and cAMP-dependent protein kinase (PKA).•Activation of PKA stimulates Ca2+ influx through T- and L-type Ca2+ channels, and cortisol production.

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-HT4 receptors in human adrenocortical cells. Our results show that 5-HT4 receptors are present in the outer adrenal cortex, both in glomerulosa and fasciculata zonae. In the zona glomerulosa. 5-HT4 receptor was detected both in immunopositive and immunonegative cells for 11β-hydroxylase, an enzyme involved in cortisol synthesis. The data demonstrate that 5-HT4 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.

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