Pituitary adenylate cyclase-activating polypeptide receptor (PACAP receptor) (PACAP receptor)

Pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are a group of Class B G protein-coupled receptors (GPCRs) comprising PAC1, VPAC1, and VPAC2 (IUPHAR/BPS Guide to Pharmacology). The PAC1 receptor is highly selective for PACAP, whereas VPAC1 and VPAC2 bind both PACAP and vasoactive intestinal peptide (VIP) with similar affinity (UniProt P41586). These receptors are widely distributed in the central and peripheral nervous systems, mediating functions such as neuroprotection, circadian rhythm regulation, and the stress response (PubMed: 26855427). In the periphery, they play roles in vasodilation and glucose-induced insulin secretion (PubMed: 22403164). PACAP receptors are major therapeutic targets for migraine, as PACAP-38 levels are elevated during attacks and its infusion can trigger migraine-like symptoms; consequently, blocking the PAC1 receptor or the PACAP ligand is a key clinical strategy (Lundbeck, Lu AG09222; Amgen, AMG 301). They are also investigated for roles in post-traumatic stress disorder (PTSD) and neurodegenerative diseases due to their potent cytoprotective and anti-inflammatory properties (PubMed: 21346760).

Other names

PAC1 receptorVPAC1 receptorVPAC2 receptorADCYAP1R1VIPR1VIPR2Pituitary adenylate cyclase-activating polypeptide type I receptorVasoactive intestinal polypeptide receptor

PAC1 receptor antagonism, PACAP ligand neutralization, and VPAC receptor agonism (Lundbeck; Amgen; IUPHAR/BPS).