Cellular mechanisms underlying pituitary adenylate cyclase activating polypeptide-stimulated secretion in the adrenal...

The adrenal medulla is a key effector of the sympathetic nervous system in the periphery. Its primary function is to translate variations in sympathetic activity into hormone outputs that modify end organ function throughout the body. These hormones include epinephrine, norepinephrine, and a variety of vasoactive peptides. Hormone secretion occurs when neurotransmitters, delivered by sympathetic nerves, bind to, and activate receptors on adrenomedullary chromaffin cells. In this context, two neurotransmitters of particular importance are acetylcholine (ACh) and pituitary adenylate cyclase activating polypeptide (PACAP). PACAP, discovered initially as a secretagogue in the hypothalamus, is now appreciated to provoke a strong secretory response from chromaffin cells in vitro and in situ. However, the cellular mechanisms underlying PACAP-stimulated secretion are still poorly understood. In the sections below, we will summarize what is known about the actions of PACAP in the adrenal medulla, discuss recent advances that pertain to the PACAP signaling pathway, and highlight areas for future investigation.