Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are prominent neuropeptides that are structurally related. Two receptors have similarly high affinity for VIP and PACAP and have therefore been termed VIP and PACAP receptor 1 (VPAC1) and VIP and PACAP receptor 2 (VPAC2). VPAC2 (also known as vasoactive intestinal peptide receptor 2) belongs to the Class II family of G-protein coupled receptors¹. A distinct feature of class II GPCRs is the presence of large N-terminal extracellular domains which contain 10 highly conserved amino acids including six cysteines, putative N terminal leader sequences and several potential N-glycosylation sites¹.

VPAC2 receptor is expressed in the uterus, prostate, smooth muscle of the gastrointestinal tract, seminal vesicles and skin, blood vessels and thymus². VPAC2 is also expressed in various brain regions including the thalamus and the suprachiasmatic nuclei (SCN)³.

VPAC2 plays important roles in the control of mammalian circadian rhythms in the SCN. Mice lacking VPAC2 show altered circadian rhythms in locomotor behavior, neuronal firing and clock gene expression⁴. Recent studies have also shown that duplication of the VPAC2 gene, and the resulting higher than normal VPAC2 signaling in patients confers a significant risk to schizophrenia⁵.