Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR Review 1

Anthony J. Harmar, Jan Fahrenkrug, Illana Gozes, Marc Laburthe, Victor May, Joseph R. Pisegna, David Vaudry, Hubert Vaudry, James A. Waschek, Sami I. Said

Research output: Contribution to journalReview articlepeer-review


Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are members of a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, gastric inhibitory peptide (GIP) and growth hormone-releasing hormone (GHRH). VIP and PACAP exert their actions through three GPCRs - PAC 1, VPAC 1 and VPAC 2- belonging to class B (also referred to as class II, or secretin receptor-like GPCRs). This family comprises receptors for all peptides structurally related to VIP and PACAP, and also receptors for parathyroid hormone, corticotropin-releasing factor, calcitonin and related peptides. PAC 1 receptors are selective for PACAP, whereas VPAC 1 and VPAC 2 respond to both VIP and PACAP with high affinity. VIP and PACAP play diverse and important roles in the CNS, with functions in the control of circadian rhythms, learning and memory, anxiety and responses to stress and brain injury. Recent genetic studies also implicate the VPAC 2 receptor in susceptibility to schizophrenia and the PAC 1 receptor in post-traumatic stress disorder. In the periphery, VIP and PACAP play important roles in the control of immunity and inflammation, the control of pancreatic insulin secretion, the release of catecholamines from the adrenal medulla and as co-transmitters in autonomic and sensory neurons. This article, written by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittee on receptors for VIP and PACAP, confirms the existing nomenclature for these receptors and reviews our current understanding of their structure, pharmacology and functions and their likely physiological roles in health and disease. More detailed information has been incorporated into newly revised pages in the IUPHAR database ().

Original languageEnglish
Pages (from-to)4-17
Number of pages14
JournalBritish Journal of Pharmacology
Issue number1
StatePublished - May 2012


  • PAC receptor
  • VIP
  • VPAC receptor
  • VPAC receptor
  • accessory proteins
  • agonists and antagonists
  • class B GPCR
  • signal transduction
  • splice variant


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