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Gene Review

VIP  -  vasoactive intestinal peptide

Homo sapiens

Synonyms: VIP peptides
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Disease relevance of VIP


Psychiatry related information on VIP

  • AIDS dementia results from interference of gp120, present on the HIV envelope protein, with normal VIP-ergic neurotrophic effects, and effects on cerebral blood flow [2].
  • It is proposed that neuronal VIP, SP, enkephalin, and NPY may serve to modulate the motor activity of the LES and that the pig is a suitable experimental animal for the study of regulatory peptides and LES functions [4].
  • There were no significant differences from the normal in the overall concentrations of either VIP or CCK in any of the psychiatric groups examined, although differences in Alzheimer's disease were apparent when cases were grouped according to postmortem delay [5].
  • Cholecystokinin, vasoactive intestinal peptide and peptide histidine methionine responses to feeding in anorexia nervosa [6].
  • CONCLUSION: Iodine-123-VIP receptor scanning has the potential to offer additional information to augment diagnostic standard methods and could influence the decision-making process in the treatment of pancreatic cancer [7].

High impact information on VIP


Chemical compound and disease context of VIP


Biological context of VIP

  • Like VIP, PACAP also stimulated 5' cyclic adenosine monophosphate (cAMP) production and the phosphorylation of cellular proteins known to be substrates for cAMP-dependent protein kinase [17].
  • The receptors for GHRH antagonists on CAKI-1 tumors are distinct from binding sites detected with (125)I-VIP (K(d) = 0.89 +/- 0.14 nM; B(max) = 183.5 +/- 2.6 fmol/mg of protein) and also have different characteristics from GHRH receptors on rat pituitary as documented by the insignificant binding of [His(1),(125)I-Tyr(10), Nle(27)]hGHRH(1-32)NH(2) [18].
  • The attenuation of tumor proliferation is receptor mediated, as VIPhyb inhibited specific 125I-labeled VIP binding to cell lines NCI-H157 and NCI-H838 with an IC50 of 0.7 microM [19].
  • CGRP was shown to increase both cell number and DNA synthesis, whereas NKA, NPY, and VIP were ineffective [20].
  • VIP stimulated adenylate cyclase activity in membranes obtained from cultured keratinocytes in a dose-dependent manner, indicating an involvement of cAMP as second messenger in this reaction [21].

Anatomical context of VIP


Associations of VIP with chemical compounds


Physical interactions of VIP

  • (iv) Taking into account the constraints provided by photoaffinity, VIP was docked into the hVPAC1 receptor N-ted [26].
  • LIF treatment of primary sympathetic neurons also induced binding of a STAT-containing protein complex to the VIP CyRE [27].
  • It is suggested that the characteristics of the vascular VIP binding sites and the close correlation between the binding and vasorelaxant properties of VIP and its related peptides argue for the vascular binding sites being functional receptors for VIP [28].
  • Nonradioactive Ro 25-1392 was as potent a competitive inhibitor as VIP for the binding of 125I-VIP to VIPR2 transfectants (Ki = 9.6 +/- 1.0 and 16 +/- 1.7 nM, respectively; mean +/- S.E.M., n = 4) [29].
  • In conclusion, this study clearly demonstrates the expression of VIP/PACAP common receptors associated with alpha s protein in human prostate and suggests that these neuropeptides could play an important and complex role in the physiology and pathophysiology of this human gland [30].

Enzymatic interactions of VIP

  • Both VIP and PACAP(1-27) were cleaved by NEP, but PACAP(1-38) was not [31].
  • Tryptase hydrolyzes VIP rapidly at several sites (Arg12, Arg14, Lys20, and Lys21) with an overall kcat/Km of 1.5 x 10(5) M-1 s-1 and hydrolyzes PHM primarily at a single site (Lys20) with a kcat/Km of 1.9 x 10(4) M-1 s-1 [32].

Co-localisations of VIP


Regulatory relationships of VIP


Other interactions of VIP


Analytical, diagnostic and therapeutic context of VIP

  • Radioiodinated VIP was purified by high-pressure liquid chromatography and administered as a single intravenous bolus injection (300 pmol [1 microgram]) [1].
  • Northern blot analysis and radioimmunoassays have shown VIP mRNA and VIP-like immunoreactivity in NSCLC cells [19].
  • RT-PCR primers were constructed for the VIP, VIPRI, and VIPRII genes as well as for megakaryocyte specific genes, c-mpl and platelet factor 4 (PF-4) [25].
  • Quantitative electron microscope autoradiography showed that after binding at the cell surface, VIP is internalized in heterogeneous endosomes [41].
  • After culturing PDC with VIP and CpG oligodeoxynucleotides for 48 h, expression of surface molecules with significance for PDC-T cell interactions as well as IFN-alpha secretion were quantified using FACS analysis and ELISA, respectively [42].


  1. Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors. Virgolini, I., Raderer, M., Kurtaran, A., Angelberger, P., Banyai, S., Yang, Q., Li, S., Banyai, M., Pidlich, J., Niederle, B., Scheithauer, W., Valent, P. N. Engl. J. Med. (1994) [Pubmed]
  2. AIDS and its dementia as a neuropeptide disorder: role of VIP receptor blockade by human immunodeficiency virus envelope. Pert, C.B., Smith, C.C., Ruff, M.R., Hill, J.M. Ann. Neurol. (1988) [Pubmed]
  3. Structural and functional analysis of the human vasoactive intestinal peptide receptor glycosylation. Alteration of receptor function by wheat germ agglutinin. Chochola, J., Fabre, C., Bellan, C., Luis, J., Bourgerie, S., Abadie, B., Champion, S., Marvaldi, J., el Battari, A. J. Biol. Chem. (1993) [Pubmed]
  4. Regulatory peptides in lower esophageal sphincter of pig and man. Aggestrup, S., Uddman, R., Jensen, S.L., Håkanson, R., Sundler, F., Schaffalitzky de Muckadell, O., Emson, P. Dig. Dis. Sci. (1986) [Pubmed]
  5. Neuropeptides in Alzheimer's disease, depression and schizophrenia. A post mortem analysis of vasoactive intestinal peptide and cholecystokinin in cerebral cortex. Perry, R.H., Dockray, G.J., Dimaline, R., Perry, E.K., Blessed, G., Tomlinson, B.E. J. Neurol. Sci. (1981) [Pubmed]
  6. Cholecystokinin, vasoactive intestinal peptide and peptide histidine methionine responses to feeding in anorexia nervosa. Harty, R.F., Pearson, P.H., Solomon, T.E., McGuigan, J.E. Regul. Pept. (1991) [Pubmed]
  7. Iodine-123-vasoactive intestinal peptide receptor scanning in patients with pancreatic cancer. Raderer, M., Kurtaran, A., Yang, Q., Meghdadi, S., Vorbeck, F., Hejna, M., Angelberger, P., Kornek, G., Pidlich, J., Scheithauer, W., Virgolini, I. J. Nucl. Med. (1998) [Pubmed]
  8. Absence of immunoreactive vasoactive intestinal polypeptide in tissue from the lungs of patients with asthma. Ollerenshaw, S., Jarvis, D., Woolcock, A., Sullivan, C., Scheibner, T. N. Engl. J. Med. (1989) [Pubmed]
  9. VIP and the pancreatic cholera syndrome. Verdin, E.M., Green, F.W. N. Engl. J. Med. (1984) [Pubmed]
  10. Pancreatic cholera: benefical effects of treatment with streptozotocin. Kahn, C.R., Levy, A.G., Gardner, J.D., Miller, J.V., Gorden, P., Schein, P.S. N. Engl. J. Med. (1975) [Pubmed]
  11. Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide. Brenneman, D.E., Westbrook, G.L., Fitzgerald, S.P., Ennist, D.L., Elkins, K.L., Ruff, M.R., Pert, C.B. Nature (1988) [Pubmed]
  12. Vasoactive intestinal peptide receptor regulation and reversible desensitization in human colonic carcinoma cells in culture. Boissard, C., Marie, J.C., Hejblum, G., Gespach, C., Rosselin, G. Cancer Res. (1986) [Pubmed]
  13. Solubilization of the active vasoactive intestinal peptide receptor from human colonic adenocarcinoma cells. el Battari, A., Martin, J.M., Luis, J., Pouzol, O., Secchi, J., Marvaldi, J., Pichon, J. J. Biol. Chem. (1988) [Pubmed]
  14. Peptide immunoreactive neurons in the human retina. Tornqvist, K., Ehinger, B. Invest. Ophthalmol. Vis. Sci. (1988) [Pubmed]
  15. Inhibition of PC-3 human prostate cancers by analogs of growth hormone-releasing hormone (GH-RH) endowed with vasoactive intestinal peptide (VIP) antagonistic activity. Plonowski, A., Varga, J.L., Schally, A.V., Krupa, M., Groot, K., Halmos, G. Int. J. Cancer (2002) [Pubmed]
  16. Effect of inhibiting N-glycosylation or oligosaccharide processing on vasoactive intestinal peptide receptor binding activity and structure. el Battari, A., Forget, P., Fouchier, F., Pic, P. Biochem. J. (1991) [Pubmed]
  17. Pituitary adenylate cyclase-activating polypeptide stimulates secretion in T84 cells. Nguyen, T.D., Heintz, G.G., Cohn, J.A. Gastroenterology (1992) [Pubmed]
  18. Human renal cell carcinoma expresses distinct binding sites for growth hormone-releasing hormone. Halmos, G., Schally, A.V., Varga, J.L., Plonowski, A., Rekasi, Z., Czompoly, T. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  19. A vasoactive intestinal peptide antagonist inhibits non-small cell lung cancer growth. Moody, T.W., Zia, F., Draoui, M., Brenneman, D.E., Fridkin, M., Davidson, A., Gozes, I. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  20. Calcitonin gene-related peptide stimulates proliferation of human endothelial cells. Haegerstrand, A., Dalsgaard, C.J., Jonzon, B., Larsson, O., Nilsson, J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  21. Vasoactive intestinal polypeptide stimulates cell proliferation and adenylate cyclase activity of cultured human keratinocytes. Haegerstrand, A., Jonzon, B., Dalsgaard, C.J., Nilsson, J. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  22. Cloning and expression of the human vasoactive intestinal peptide receptor. Sreedharan, S.P., Robichon, A., Peterson, K.E., Goetzl, E.J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  23. Vasoactive intestinal peptide generates human tolerogenic dendritic cells that induce CD4 and CD8 regulatory T cells. Gonzalez-Rey, E., Chorny, A., Fernandez-Martin, A., Ganea, D., Delgado, M. Blood (2006) [Pubmed]
  24. Peptidergic innervation of human epicardial coronary arteries. Gulbenkian, S., Saetrum Opgaard, O., Ekman, R., Costa Andrade, N., Wharton, J., Polak, J.M., Queiroz e Melo, J., Edvinsson, L. Circ. Res. (1993) [Pubmed]
  25. Characterization of vasoactive intestinal peptide receptors on human megakaryocytes and platelets. Park, S.K., Olson, T.A., Ercal, N., Summers, M., O'Dorisio, M.S. Blood (1996) [Pubmed]
  26. Peptide Agonist Docking in the N-terminal Ectodomain of a Class II G Protein-coupled Receptor, the VPAC1 Receptor: PHOTOAFFINITY, NMR, AND MOLECULAR MODELING. Tan, Y.V., Couvineau, A., Murail, S., Ceraudo, E., Neumann, J.M., Lacapère, J.J., Laburthe, M. J. Biol. Chem. (2006) [Pubmed]
  27. STAT proteins participate in the regulation of the vasoactive intestinal peptide gene by the ciliary neurotrophic factor family of cytokines. Symes, A., Lewis, S., Corpus, L., Rajan, P., Hyman, S.E., Fink, J.S. Mol. Endocrinol. (1994) [Pubmed]
  28. Characterization of functional receptors for vasoactive intestinal peptide in bovine cerebral arteries. Suzuki, Y., McMaster, D., Huang, M., Lederis, K., Rorstad, O.P. J. Neurochem. (1985) [Pubmed]
  29. Novel cyclic peptide agonist of high potency and selectivity for the type II vasoactive intestinal peptide receptor. Xia, M., Sreedharan, S.P., Bolin, D.R., Gaufo, G.O., Goetzl, E.J. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  30. Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptors in human benign hyperplastic prostate. Solano, R.M., Carmena, M.J., Carrero, I., Cavallaro, S., Roman, F., Hueso, C., Travali, S., Lopez-Fraile, N., Guijarro, L.G., Prieto, J.C. Endocrinology (1996) [Pubmed]
  31. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP-27, but not PACAP-38) degradation by the neutral endopeptidase EC Gourlet, P., Vandermeers, A., Robberecht, P., Deschodt-Lanckman, M. Biochem. Pharmacol. (1997) [Pubmed]
  32. Degradation of airway neuropeptides by human lung tryptase. Tam, E.K., Caughey, G.H. Am. J. Respir. Cell Mol. Biol. (1990) [Pubmed]
  33. Pituitary adenylate cyclase-activating polypeptide, helospectin, and vasoactive intestinal polypeptide in human corpus cavernosum. Hedlund, P., Alm, P., Ekström, P., Fahrenkrug, J., Hannibal, J., Hedlund, H., Larsson, B., Andersson, K.E. Br. J. Pharmacol. (1995) [Pubmed]
  34. Neurons that express the AMPA receptor GluR2/3 subunits in suprachiasmatic nuclei of Syrian hamsters colocalize either vasoactive intestinal peptide, peptide histidine isoleucine or gastrin-releasing peptide. Peytevin, J., Aïoun, J., Chambille, I. Cell Tissue Res. (2000) [Pubmed]
  35. Cross-competition between vasoactive intestinal peptide and somatostatin for binding to tumor cell membrane receptors. Virgolini, I., Yang, Q., Li, S., Angelberger, P., Neuhold, N., Niederle, B., Scheithauer, W., Valent, P. Cancer Res. (1994) [Pubmed]
  36. Vasoactive intestinal peptide synergizes with TNF-alpha in inducing human dendritic cell maturation. Delneste, Y., Herbault, N., Galea, B., Magistrelli, G., Bazin, I., Bonnefoy, J.Y., Jeannin, P. J. Immunol. (1999) [Pubmed]
  37. Vasoactive intestinal peptide enhances immunoglobulin production and growth in human plasma cells via mechanisms that may involve protein kinase C. Kimata, H., Yoshida, A., Ishioka, C., Fujimoto, M., Furusho, K. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  38. Distributions of neuropeptides in the human esophagus. Wattchow, D.A., Furness, J.B., Costa, M., O'Brien, P.E., Peacock, M. Gastroenterology (1987) [Pubmed]
  39. Localization of receptors for vasoactive intestinal peptide, somatostatin, and substance P in distinct compartments of human lymphoid organs. Reubi, J.C., Horisberger, U., Kappeler, A., Laissue, J.A. Blood (1998) [Pubmed]
  40. Differential expression of vasoactive intestinal peptide and its functional receptors in human osteoarthritic and rheumatoid synovial fibroblasts. Juarranz, Y., Gutiérrez-Cañas, I., Santiago, B., Carrión, M., Pablos, J.L., Gomariz, R.P. Arthritis Rheum. (2008) [Pubmed]
  41. Combined ultrastructural and biochemical study of cellular processing of vasoactive intestinal peptide and its receptors in human colonic carcinoma cells in culture. Hejblum, G., Gali, P., Boissard, C., Astesano, A., Marie, J.C., Anteunis, A., Hui Bon Hoa, D., Rosselin, G. Cancer Res. (1988) [Pubmed]
  42. Human Plasmacytoid Dendritic Cell Function: Inhibition of IFN-{alpha} Secretion and Modulation of Immune Phenotype by Vasoactive Intestinal Peptide. Fabricius, D., O'dorisio, M.S., Blackwell, S., Jahrsd??rfer, B. J. Immunol. (2006) [Pubmed]
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