VPAC1 Receptor

VPAC1 receptor (VIPR1) is a class B G protein-coupled receptor that binds vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) with comparable affinity and mediates diverse physiological functions in the nervous, endocrine, and immune systems^[1][2][3]. Mechanistically, VPAC1 participates in neuropeptide-driven signal transduction through pathways that regulate exocrine and endocrine secretion, smooth muscle relaxation, immune responses, and inflammatory processes^[1][4]. Structural and pharmacological studies have identified the N-terminal extracellular domain as a critical determinant of ligand recognition, where interactions between VIP and the receptor ectodomain govern receptor activation and downstream signaling^[1]. In disease-relevant contexts, VPAC1 is expressed in multiple human tissues and has been detected in a broad range of human tumors, supporting its utility as a molecular target for receptor localization, tumor characterization, and peptide-based translational research^[5]. Compared with related receptor isoforms, VPAC1 and VPAC2 recognize both VIP and PACAP with similar affinity, whereas PAC1 displays markedly higher affinity and potency for PACAP than for VIP, providing an important pharmacological distinction for receptor-selective experimental design^[2][3][6]. For research applications, ongoing efforts to develop selective ligands, fluorescent peptide probes, and structure-guided receptor modulators have improved the investigation of VPAC1 signaling, receptor internalization, ligand selectivity, and therapeutic targeting strategies^[1][7][8].