Regulation of catecholamine production from the Adrenal Medulla

The circulating catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) derive from two major sources in the whole organism: the sympathetic nerve endings, which release norepinephrine on effector organs, and the chromaffin cells of the adrenal medulla, which are cells that synthesize, store and release epinephrine (mainly) and norepinephrine upon acetylcholine stimulation of the nicotinic cholinergic receptors (nAChRs) present on their membranes. Thus, the chromaffin cells of the adrenal medulla function, in essence, as postganglionic sympathetic neurons and constitute the major source of circulating epinephrine in the body. All of the epinephrine in the body and a significant amount of circulating norepinephrine derive from the adrenal medulla. The secretion of catecholamines from adrenal chromaffin cells is regulated in a complex way by a variety of membrane receptors present in these cells. Most of these receptors are G protein-coupled receptors (GPCRs), including adrenergic receptors (ARs), which act as “presynaptic autoreceptors” in this regard. The majority of hormones and of the receptors they activate on chromaffin cell membranes stimulate catecholamine secretion, with the notable exception of the α2ARs, which inhibit catecholamine secretion (inhibitory presynaptic autoreceptors). The present chapter will discuss the molecular mechanisms by which all of these receptors regulate catecholamine synthesis and secretion by the chromaffin cells of the adrenal medulla, highlighting significant gaps in the knowledge requiring future research to fill them.