VPAC2 receptor

Pituitary adenylyl cyclase-activating polypeptide receptor VPAC2 (VIPR2) is a class B G protein-coupled receptor that binds both vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating polypeptide (PACAP) with high affinity and primarily activates adenylyl cyclase-dependent signaling pathways^[1][2]. VPAC2 participates in neuroendocrine regulation, circadian rhythm synchronization, immune modulation, and metabolic control through cAMP-mediated intracellular signaling cascades^[1][3]. Mechanistically, VPAC2 belongs to the PACAP/VIP receptor family together with VPAC1 and PAC1; however, unlike PAC1, which displays marked preference for PACAP, VPAC2 recognizes VIP and PACAP with comparable affinity, providing a distinct signaling profile and physiological function^[2][4]. In experimental systems, VPAC2 signaling has been implicated in central nervous system development and neuroprotection, and VPAC2 receptor activation mediates VIP-induced protection against neonatal excitotoxic brain injury in mice^[5]. Genetic and pharmacological studies further associate VPAC2-regulated signaling with circadian clock function and neuropsychiatric phenotypes, supporting its relevance in neurological disease models^[3][6]. Beyond the nervous system, VPAC2 is expressed in pancreatic islets and contributes to peptide-mediated regulation of insulin and glucagon secretion, linking receptor activity to metabolic homeostasis^[7]. For experimental applications, selective VPAC2 agonists have been developed and are widely used to investigate receptor-specific signaling, cellular responses, and therapeutic potential within the VIP/PACAP receptor network^[8].