Pharmacological profile of serotonergic receptors in the adrenal gland

The secretory activity of the adrenal gland is mainly regulated by peptidergic hormones (ACTH, angiotensin II) and ions. However, there is now increasing evidence that local factors, including neuropeptides and neurotransmitters, can also participate in the control of adrenocortical cells. In particular, serotonin (5-HT), produced by adrenochromaffin cells in frog and rat as well as by mast cells in the adrenal gland of rat and human, stimulates corticosteroid secretion. In both frog and human adrenal gland, the benzamide derivative (R,S)-zacopride induces a robust increase in corticosteroid release suggesting that the effect of 5-HT on steroidogenesis is mediated through activation of 5-HT4 receptors. In contrast, in rat, the stimulatory effect of 5-HT on aldosterone secretion is clearly not mediated by 5-HT4 receptors. In all three species, incubation of adrenocortical fragments with 5-HT induces a significant increase in cAMP formation. Our data suggest that 5-HT, released within the adrenal cortex, may act as a paracrine factor to stimulate steroid secretion. Although the corticotropic effect of 5-HT has been conserved from amphibians to primates, the type of receptors involved in the action of 5-HT markedly differs across species.