VIPR2 explained

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]

Function

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. 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

• Vasoactive intestinal peptide receptor
• VIPR1

Further reading

• Goetzl EJ, Pankhaniya RR, Gaufo GO, etal . Selectivity of effects of vasoactive intestinal peptide on macrophages and lymphocytes in compartmental immune responses. . Ann. N. Y. Acad. Sci. . 840 . 1 NEUROIMMUNOMO. 540–50 . 1998 . 9629281 . 10.1111/j.1749-6632.1998.tb09593.x . 1998NYASA.840..540G . 11871747 .
• Adamou JE, Aiyar N, Van Horn S, Elshourbagy NA . Cloning and functional characterization of the human vasoactive intestinal peptide (VIP)-2 receptor. . Biochem. Biophys. Res. Commun. . 209 . 2 . 385–92 . 1995 . 7733904 . 10.1006/bbrc.1995.1515 .
• Svoboda M, Tastenoy M, Van Rampelbergh J, etal . Molecular cloning and functional characterization of a human VIP receptor from SUP-T1 lymphoblasts. . Biochem. Biophys. Res. Commun. . 205 . 3 . 1617–24 . 1995 . 7811244 . 10.1006/bbrc.1994.2852 .
• Inagaki N, Yoshida H, Mizuta M, etal . Cloning and functional characterization of a third pituitary adenylate cyclase-activating polypeptide receptor subtype expressed in insulin-secreting cells. . Proc. Natl. Acad. Sci. U.S.A. . 91 . 7 . 2679–83 . 1994 . 8146174 . 10.1073/pnas.91.7.2679. 43433 . 1994PNAS...91.2679I . free .
• Xia M, Gaufo GO, Wang Q, etal . Transduction of specific inhibition of HuT 78 human T cell chemotaxis by type I vasoactive intestinal peptide receptors. . J. Immunol. . 157 . 3 . 1132–8 . 1996 . 10.4049/jimmunol.157.3.1132 . 8757618 . 40867208 . free .
• Wei Y, Mojsov S . Tissue specific expression of different human receptor types for pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide: implications for their role in human physiology. . J. Neuroendocrinol. . 8 . 11 . 811–7 . 1997 . 8933357 . 10.1046/j.1365-2826.1996.05191.x . 22302790 .
• Mackay M, Fantes J, Scherer S, etal . Chromosomal localization in mouse and human of the vasoactive intestinal peptide receptor type 2 gene: a possible contributor to the holoprosencephaly 3 phenotype. . Genomics . 37 . 3 . 345–53 . 1997 . 8938447 . 10.1006/geno.1996.0569 .
• Nicole P, Du K, Couvineau A, Laburthe M . Site-directed mutagenesis of human vasoactive intestinal peptide receptor subtypes VIP1 and VIP2: evidence for difference in the structure-function relationship. . J. Pharmacol. Exp. Ther. . 284 . 2 . 744–50 . 1998 . 9454823 .
• Dewit D, Gourlet P, Amraoui Z, etal . The vasoactive intestinal peptide analogue RO25-1553 inhibits the production of TNF and IL-12 by LPS-activated monocytes. . Immunol. Lett. . 60 . 1 . 57–60 . 1998 . 9541464 . 10.1016/S0165-2478(97)00129-6 .
• Lutz EM, Shen S, Mackay M, etal . Structure of the human VIPR2 gene for vasoactive intestinal peptide receptor type 2. . FEBS Lett. . 458 . 2 . 197–203 . 1999 . 10481065 . 10.1016/S0014-5793(99)01135-7 . 20.500.11820/4a02420b-ff08-47b1-a44f-42cb7b326647 . 27842682 . free .
• Busto R, Prieto JC, Bodega G, etal . Immunohistochemical localization and distribution of VIP/PACAP receptors in human lung. . Peptides . 21 . 2 . 265–9 . 2000 . 10764955 . 10.1016/S0196-9781(99)00202-8 . 44951090 .
• Nicole P, Lins L, Rouyer-Fessard C, etal . Identification of key residues for interaction of vasoactive intestinal peptide with human VPAC1 and VPAC2 receptors and development of a highly selective VPAC1 receptor agonist. Alanine scanning and molecular modeling of the peptide. . J. Biol. Chem. . 275 . 31 . 24003–12 . 2000 . 10801840 . 10.1074/jbc.M002325200 . free .
• Bajo AM, Juarranz MG, Valenzuela P, etal . Expression of vasoactive intestinal peptide (VIP) receptors in human uterus. . Peptides . 21 . 9 . 1383–8 . 2001 . 11072126 . 10.1016/S0196-9781(00)00282-5 . 429907 .
• Lara-Marquez M, O'Dorisio M, O'Dorisio T, etal . Selective gene expression and activation-dependent regulation of vasoactive intestinal peptide receptor type 1 and type 2 in human T cells. . J. Immunol. . 166 . 4 . 2522–30 . 2001 . 11160313 . 10.4049/jimmunol.166.4.2522. free .
• Lara-Marquez ML, O'Dorisio MS, Karacay B . Vasoactive intestinal peptide (VIP) receptor type 2 (VPAC2) is the predominant receptor expressed in human thymocytes. . Ann. N. Y. Acad. Sci. . 921 . 1. 45–54 . 2001 . 11193874 . 10.1111/j.1749-6632.2000.tb06950.x . 8156918 .
• Groneberg DA, Hartmann P, Dinh QT, Fischer A . Expression and distribution of vasoactive intestinal polypeptide receptor VPAC(2) mRNA in human airways. . Lab. Invest. . 81 . 5 . 749–55 . 2001 . 11351046 . 10.1038/labinvest.3780283 . free .
• Juarranz MG, Bolaños O, Gutiérrez-Cañas I, etal . Neuroendocrine differentiation of the LNCaP prostate cancer cell line maintains the expression and function of VIP and PACAP receptors. . Cell. Signal. . 13 . 12 . 887–94 . 2002 . 11728828 . 10.1016/S0898-6568(01)00199-1 .
• Fischer TC, Dinh QT, Peiser C, etal . Simultaneous detection of receptor mRNA and ligand protein in human skin tissues. . J. Cutan. Pathol. . 29 . 2 . 65–71 . 2002 . 12150135 . 10.1034/j.1600-0560.2002.290201.x . 22886240 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .

External links

• Web site: VIP and PACAP Receptors: VPAC₂ . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 12 December 2008 . 3 March 2016 . https://web.archive.org/web/20160303205921/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2451 . dead .

Notes and References

1. Web site: Entrez Gene: VIPR2 vasoactive intestinal peptide receptor 2. live. https://web.archive.org/web/20101205081110/http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene. 5 December 2010. dmy-all.
2. Reubi JC . In vitro evaluation of VIP/PACAP receptors in healthy and diseased human tissues. Clinical implications. . Ann N Y Acad Sci . 921 . 1. 1–25 . 2000 . 11193811 . 10.1111/j.1749-6632.2000.tb06946.x . 2000NYASA.921....1R . 21204750 .
3. Reubi JC, Laderach U, Waser B, Gebbers JO, Robberecht P, Laissue JA . Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin. . Cancer Res . 60 . 11. 3105–3112 . 2000 . 10850463 .
4. Basille M, Cartier D, Vaudry D, Lihrmann I, Fournier A, Freger P, Gallo-Payet N, Vaudry H, Gonzalez B . Localization and characterization of pituitary adenylate cyclase-activating polypeptide receptors in the human cerebellum during development . J. Comp. Neurol. . 496 . 4 . 468–78 . June 2006 . 16572459 . 10.1002/cne.20934 . 9385702 .
5. Web site: IUPHAR-DB VPAC2 receptor Redirect. www.iuphar-db.org. 7 May 2018. live. https://web.archive.org/web/20160303204518/http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=372. 3 March 2016. dmy-all.
6. Juarranz Y, Gutiérrez-Cañas I, Santiago B, Carrión M, Pablos JL, Gomariz RP . Differential expression of vasoactive intestinal peptide and its functional receptors in human osteoarthritic and rheumatoid synovial fibroblasts . Arthritis Rheum. . 58 . 4 . 1086–95 . April 2008 . 18383383 . 10.1002/art.23403 . free .
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 . The VPAC2 receptor is essential for circadian function in the mouse suprachiasmatic nuclei. . Cell . 109 . 4. 497–508 . 2002 . 12086606 . 10.1016/S0092-8674(02)00736-5 . 18583905 . free .
8. Cutler DJ, Haraura M, Reed HE, Shen S, Sheward WJ, Morrison CF, Marston HM, Harmar AJ, Piggins HD . The mouse VPAC2 receptor confers suprachiasmatic nuclei cellular rhythmicity and responsiveness to vasoactive intestinal polypeptide in vitro . Eur. J. Neurosci. . 17 . 2 . 197–204 . January 2003 . 12542655 . 10.1046/j.1460-9568.2003.02425.x . 2507786 .
9. Hughes AT, Fahey B, Cutler DJ, Coogan AN, Piggins HD . Aberrant gating of photic input to the suprachiasmatic circadian pacemaker of mice lacking the VPAC2 receptor . J. Neurosci. . 24 . 14 . 3522–6 . April 2004 . 15071099 . 10.1523/JNEUROSCI.5345-03.2004 . 6729740 . free .
10. Asnicar MA, Köster A, Heiman ML, Tinsley F, Smith DP, Galbreath E, Fox N, Ma YL, Blum WF, Hsiung HM . 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 . October 2002 . 12239111 . 10.1210/en.2002-220354 . free .
11. Kellogg DL, Zhao JL, Wu Y, Johnson JM . VIP/PACAP receptor mediation of cutaneous active vasodilation during heat stress in humans . J. Appl. Physiol. . 109 . 1 . 95–100 . July 2010 . 20395540 . 2904198 . 10.1152/japplphysiol.01187.2009 .
12. Miller AL, Verma D, Grinninger C, Huang MC, Goetzl EJ . 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 . July 2006 . 16888203 . 1557659 . 10.1196/annals.1317.055 . 2006NYASA1070..422M .
13. Kalló I, Kalamatianos T, Wiltshire N, Shen S, Sheward WJ, Harmar AJ, Coen CW . 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 . April 2004 . 15090046 . 10.1111/j.0953-816X.2004.03335.x . 2389771 .
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 . 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. February 2011 . 21285140 . 4441324 . 10.1176/appi.ajp.2010.10060876 .
15. Zhang ZH, Wu SD, Gao H, Shi G, Jin JZ, Kong J, Tian Z, Su Y . 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 . March 2006 . 16552823 . 4124332 . 10.3748/wjg.v12.i9.1468 . free .