VPAC2

Class

neuroprotective immunomodulator peptide

VPAC2 (vasoactive intestinal peptide receptor 2) is a cell-surface receptor belonging to the G-protein-coupled receptor family. Its natural signaling molecules are vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP), two closely related neuropeptides that circulate in the nervous and immune systems. Engaging VPAC2 activates a signaling cascade that raises levels of the intracellular messenger cyclic AMP, which in turn influences gene expression, cell survival pathways, and cytokine production. Because VPAC2 is expressed on neurons, glial cells, and immune cells such as T lymphocytes and macrophages, modulating it has been explored for conditions where nervous system damage and inappropriate immune activation coexist, including autoimmune and neuroinflammatory disorders and states of acute neuronal injury. The therapeutic rationale is that selectively engaging VPAC2, rather than the broader VIP receptor family, can shift immune cells toward a less inflammatory profile while simultaneously supporting neuronal survival, offering a dual neuroprotective and immunomodulatory effect. This receptor also participates in circadian rhythm regulation and insulin secretion, reflecting its wide tissue distribution and the breadth of physiological processes VIP-family peptides influence.