M 3 -subtype muscarinic receptor activation stimulates intracellular calcium oscillations and aldosterone production in human adrenocortical HAC15 cells.

A previous body of work in bovine and rodent models shows that cholinergic agonists modulate the secretion of steroid hormones from the adrenal cortex. In this study we used live-cell Ca ²⁺ imaging to investigate cholinergic activity in the HAC15 human adrenocortical carcinoma cell line. The cholinergic agonists carbachol and acetylcholine triggered heterogeneous Ca ²⁺ oscillations that were strongly inhibited by antagonists with high affinity for the M ₃ muscarinic receptor subtype, while preferential block of M ₁ or M ₂ receptors was less effective. Acute exposure to carbachol and acetylcholine modestly elevated aldosterone secretion in HAC15 cells, and this effect was also diminished by M ₃ inhibition. HAC15 cells expressed relatively high levels of mRNA for M ₃ and M ₂ receptors, while M ₁ and M ₅ mRNA were much lower. In conclusion, our data extend previous findings in non-human systems to implicate the M ₃ receptor as the dominant muscarinic receptor in the human adrenal cortex.
(Copyright © 2018. Published by Elsevier B.V.)