Vasointestinal peptide (VIP) and pituitary adenylate cyclase–activating peptide (PACAP) belong to the glucagon hormone superfamily, which includes secretin, growth hormone–releasing hormone (GHRH), glucagon, glucagon-like peptides 1 and 2 (GLP-1 and GLP-2), peptide histidine methionine (PHM), and glucose-dependent insulinotropic polypeptide (GIP)¹. PACAP and VIP effects have been described in the digestive tract, cardiovascular system, airways, reproductive system, immune system, endocrine glands, and brain². VIP and PACAP share a common G-protein coupled receptor, VPAC1³.

VPAC1 is a membrane-associated protein and shares significant homology with members of the G-protein coupled class B receptor family, the most important of which 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 sites⁴. In the CNS, VPAC1 receptors are abundantly localized in piriform cortex, cerebral cortex, suprachiasmatic nucleus, hippocampus, and pineal gland⁵. In peripheral tissues, VPAC1 receptors have been found in breast, kidney, liver, lung, prostate, spleen, and mucosa of the gastrointestinal tract⁶. VPAC1 mediates a large array of VIP and PACAP actions on exocrine secretion, hormones release, muscle relaxation, metabolism, fetus growth, tumor cells and embryonic brain development⁷.