M-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 imaging to investigate cholinergic activity in the HAC15 human adrenocortical carcinoma cell line. The cholinergic agonists carbachol and acetylcholine triggered heterogeneous Ca oscillations that were strongly inhibited by antagonists with high affinity for the M muscarinic receptor subtype, while preferential block of M or M 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 inhibition. HAC15 cells expressed relatively high levels of mRNA for M and M receptors, while M and M mRNA were much lower. In conclusion, our data extend previous findings in non-human systems to implicate the M receptor as the dominant muscarinic receptor in the human adrenal cortex.