Vasoactive intestinal polypeptide receptor 1 (VPAC1)

Vasoactive intestinal polypeptide receptor 1 (VPAC1) is a class B1 G protein-coupled receptor widely expressed in the central nervous system, especially in the cerebral cortex and hippocampus, and peripheral tissues such as liver, lung, intestine, and immune cells. It mediates cellular effects of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP), regulating processes including neuronal survival, circadian rhythm, immune modulation, cell proliferation, and synaptic plasticity. VPAC1 activation leads primarily to stimulation of adenylyl cyclase via Gs proteins, increased cAMP, and downstream signaling through protein kinase A. VPAC1 is implicated in diverse pathologies (neurodegeneration, inflammation, cancer, cardiovascular diseases), making it an important therapeutic target, but structural similarity with related receptors poses challenges for drug selectivity and safety.

Other names

VPAC1VIP receptor 1VIP1R

Agonists/peptide mimics activate Gs protein signaling, increasing cAMP and activating protein kinase A (PKA); Allosteric modulators (e.g., ticagrelor) may block or alter receptor signaling; Inhibition of neuroinflammation via glial protein induction; Modulation of calcium channels and GABA release.