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RefSeq (mRNA)



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Vasoactive intestinal peptide receptor 2 also known as VPAC2, is a G-protein coupled receptor that in humans is encoded by the VIPR2 gene.[1]

Tissue distribution

VIPR2 is expressed in the uterus, prostate, smooth muscle of the gastrointestinal tract, seminal vesicles and skin, blood vessels and thymus.[2][3] VIPR2 is also expressed in the cerebellum.[4]


Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are homologous peptides that function as neurotransmitters and neuroendocrine hormones. While the receptors for VIP (VIRP 1 and 2) and PACAP (ADCYAP1R1) share homology, they differ in their substrate specificities and expression patterns.[1] VIPR2 transduction results in upregulation of adenylate cyclase activity.[5] Furthermore, VIPR2 mediates the anti-inflammatory effects of VIP.[6]

Research using VPAC2 knockout mice implicate it in the function of the circadian clock, growth, basal energy expenditure and male reproduction.[7][8][9][10]

VIPR2 and/or PAC1 receptor activation is involved in cutaneous active vasodilation in humans.[11]

Splice variants may modify the immunoregulatory contributions of the VIP-VIPR2 axis.[12]

VIPR2 may contribute to autoregulation and/or coupling within the suprachiasmatic nucleus (SCN) core and to control of the SCN shell.[13]

Clinical significance

VIPR2 may play a role in schizophrenia.[14]

The abnormal expression of VIPR2 messenger RNA in gallbladder tissue may play a role in the formation of gall stones and polyps.[15]

See also


  1. 1.0 1.1 "Entrez Gene: VIPR2 vasoactive intestinal peptide receptor 2". Archived from the original on 5 December 2010.
  2. Reubi JC (2000). "In vitro evaluation of VIP/PACAP receptors in healthy and diseased human tissues. Clinical implications". Ann N Y Acad Sci. 921 (1): 1–25. doi:10.1111/j.1749-6632.2000.tb06946.x. PMID 11193811.
  3. Reubi JC, Laderach U, Waser B, Gebbers JO, Robberecht P, Laissue JA (2000). "Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin". Cancer Res. 60 (11): 3105–3112. PMID 10850463.
  4. Basille M, Cartier D, Vaudry D, Lihrmann I, Fournier A, Freger P, Gallo-Payet N, Vaudry H, Gonzalez B (June 2006). "Localization and characterization of pituitary adenylate cyclase-activating polypeptide receptors in the human cerebellum during development". J. Comp. Neurol. 496 (4): 468–78. doi:10.1002/cne.20934. PMID 16572459.
  5. "IUPHAR-DB VPAC2 receptor Redirect". Archived from the original on 3 March 2016. Retrieved 7 May 2018.
  6. Juarranz Y, Gutiérrez-Cañas I, Santiago B, Carrión M, Pablos JL, Gomariz RP (April 2008). "Differential expression of vasoactive intestinal peptide and its functional receptors in human osteoarthritic and rheumatoid synovial fibroblasts". Arthritis Rheum. 58 (4): 1086–95. doi:10.1002/art.23403. PMID 18383383.
  7. Harmar AJ, Marston HM, Shen S, Spratt C, West KM, Sheward WJ, Morrison CF, Dorin JR, Piggins HD, Reubi JC, Kelly JS, Maywood ES, Hastings MH (2002). "The VPAC2 receptor is essential for circadian function in the mouse suprachiasmatic nuclei". Cell. 109 (4): 497–508. doi:10.1016/S0092-8674(02)00736-5. PMID 12086606.
  8. Cutler DJ, Haraura M, Reed HE, Shen S, Sheward WJ, Morrison CF, Marston HM, Harmar AJ, Piggins HD (January 2003). "The mouse VPAC2 receptor confers suprachiasmatic nuclei cellular rhythmicity and responsiveness to vasoactive intestinal polypeptide in vitro". Eur. J. Neurosci. 17 (2): 197–204. doi:10.1046/j.1460-9568.2003.02425.x. PMID 12542655.
  9. Hughes AT, Fahey B, Cutler DJ, Coogan AN, Piggins HD (April 2004). "Aberrant gating of photic input to the suprachiasmatic circadian pacemaker of mice lacking the VPAC2 receptor". J. Neurosci. 24 (14): 3522–6. doi:10.1523/JNEUROSCI.5345-03.2004. PMID 15071099.
  10. Asnicar MA, Köster A, Heiman ML, Tinsley F, Smith DP, Galbreath E, Fox N, Ma YL, Blum WF, Hsiung HM (October 2002). "Vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating peptide receptor 2 deficiency in mice results in growth retardation and increased basal metabolic rate". Endocrinology. 143 (10): 3994–4006. doi:10.1210/en.2002-220354. PMID 12239111.
  11. Kellogg DL, Zhao JL, Wu Y, Johnson JM (July 2010). "VIP/PACAP receptor mediation of cutaneous active vasodilation during heat stress in humans". J. Appl. Physiol. 109 (1): 95–100. doi:10.1152/japplphysiol.01187.2009. PMC 2904198. PMID 20395540.
  12. Miller AL, Verma D, Grinninger C, Huang MC, Goetzl EJ (July 2006). "Functional splice variants of the type II G protein-coupled receptor (VPAC2) for vasoactive intestinal peptide in mouse and human lymphocytes". Ann. N. Y. Acad. Sci. 1070 (1): 422–6. doi:10.1196/annals.1317.055. PMC 1557659. PMID 16888203.
  13. Kalló I, Kalamatianos T, Wiltshire N, Shen S, Sheward WJ, Harmar AJ, Coen CW (April 2004). "Transgenic approach reveals expression of the VPAC2 receptor in phenotypically defined neurons in the mouse suprachiasmatic nucleus and in its efferent target sites". Eur. J. Neurosci. 19 (8): 2201–11. doi:10.1111/j.0953-816X.2004.03335.x. PMID 15090046.
  14. Levinson DF, Duan J, Oh S, Wang K, Sanders AR, Shi J, Zhang N, Mowry BJ, Olincy A, Amin F, Cloninger CR, Silverman JM, Buccola NG, Byerley WF, Black DW, Kendler KS, Freedman R, Dudbridge F, Pe'er I, Hakonarson H, Bergen SE, Fanous AH, Holmans PA, Gejman PV (February 2011). "Copy Number Variants in Schizophrenia: Confirmation of Five Previous Findings and New Evidence for 3q29 Microdeletions and VIPR2 Duplications". Am J Psychiatry. 168 (3): 302–316. doi:10.1176/appi.ajp.2010.10060876. PMID 21285140.
  15. Zhang ZH, Wu SD, Gao H, Shi G, Jin JZ, Kong J, Tian Z, Su Y (March 2006). "Expression of pituitary adenylate cyclase-activating polypeptide 1 and 2 receptor mRNA in gallbladder tissue of patients with gallstone or gallbladder polyps". World J. Gastroenterol. 12 (9): 1468–71. PMID 16552823.

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.