Pharmacological profile of serotonergic receptors in the adrenal gland

The secretory activity of the adrenal gland is mainly regulated by peptider gic hormones (ACTH, angiotensin II) and ions. However, there is now increas ing evidence that local factors, including neuropeptides and neurotransmitt ers, can also participate in the control of adrenocortical cells. In partic ular, 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 benzami de derivative (R,S)-zacopride induces a robust increase in corticosteroid r elease suggesting that the effect of 5-HT on steroidogenesis is mediated th rough activation of 5-HT4 receptors. In contrast, in rat, the stimulatory e ffect of 5-HT on aldosterone secretion is clearly not mediated by 5-HT4 rec eptors. 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.