Multifaces of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP):From Neuroprotection and Energy Homeostasis to Respiratory andCardiovascular Systems

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) belongs to the secretin/glucagon/vasoactive intestinal peptide (VIP) family and is one of the most highly conserved neuropeptides. The effects of PACAP are mediated through three G-protein coupled receptors: PAC1R, which has specific affinity for PACAP, and VPAC1 and VPAC2 that have equal affinity for both PACAP and VIP. PACAP and PAC1R are widely expressed and distributed throughout the body, including the central nervous system, the gastro-intestinal tract, the endocrine pancreas, the respiratory and cardiovascular systems. With this widespread tissue distribution, PACAP has been shown to be a pleiotropic peptide exerting a range of physiological functions. Within the body, PACAP serves as a neurotransmitter, neuromodulator, neurotrophic factor, neuroprotectant, secretagogue, and neurohormone. In this present review, we provide current insight on the role of PACAP in neuroprotection, its role in energy homeostasis and the impact PACAP may have on respiratory and cardiovascular disease. We conclude with an outlook for the future of PACAP-related research.