Vasoactive intestinal polypeptide receptor 1 (VIPR1) (VIPR1)

Vasoactive intestinal polypeptide receptor 1 (VIPR1), also known as VPAC1, is a Class B G protein-coupled receptor that mediates the actions of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) (UniProt P32241). It is widely distributed across the central nervous system, gastrointestinal tract, and immune system, playing a critical role in smooth muscle relaxation, vasodilation, and the modulation of inflammatory responses (IUPHAR/BPS Guide to Pharmacology). In the immune system, VIPR1 signaling generally promotes an anti-inflammatory environment by suppressing pro-inflammatory cytokine production and enhancing regulatory T-cell activity (PubMed: 22503473). The receptor is notably overexpressed in several common malignancies, including lung, breast, and prostate cancers, which has led to its investigation as a target for peptide-based imaging and targeted radiotherapy (PubMed: 21813585). Therapeutic development targeting VIPR1 includes agonists like Aviptadil for respiratory distress and erectile dysfunction, though clinical utility is often constrained by dose-limiting side effects such as hypotension and secretory diarrhea (PubChem CID 11957568). Beyond oncology and inflammation, VIPR1 is involved in regulating circadian rhythms and neuroprotection, suggesting potential roles in treating neurodegenerative disorders.

Other names

VPAC1 receptorVIP receptor type 1PACAP receptor 2PACAP-R2VAPC1RHVR1

Agonist binding to VIPR1 triggers the activation of the Gs alpha subunit, which stimulates adenylate cyclase to increase intracellular cyclic adenosine monophosphate (cAMP) levels, subsequently activating protein kinase A (PKA) and other downstream signaling pathways (IUPHAR/BPS Guide to Pharmacology).