Other entities represented in this entry:
HGNC Approved Gene Symbol: VIP
Cytogenetic location: 6q25.2 Genomic coordinates (GRCh38): 6:152,750,797-152,759,760 (from NCBI)
Vasoactive intestinal peptide (VIP) is a member of the glucagon-secretin family, which includes glucagon (138030), secretin (182099), and gastric inhibitory peptide (GIP; 137240), and exhibits a wide range of biologic actions, such as relaxation of smooth muscle, stimulation of intestinal water and electrolyte secretion, and release of insulin, glucagon and several anterior pituitary hormones (summary by Itoh et al. (1983)).
By cloning the DNA sequence complementary to the mRNA coding for human vasoactive intestinal peptide (VIP), a 28-amino acid peptide originally isolated from porcine duodenum, Itoh et al. (1983) found that the VIP precursor contains not only VIP but also a novel peptide of 27 amino acids, designated PHM27, that has N-terminal histidine and C-terminal methionine. It differs from PHI17 isolated from porcine intestine by 2 amino acids; PHI27, as its designation indicates, has C-terminal isoleucine. The primary translation product of the mRNA encoding VIP (prepro-VIP) has a molecular mass of 20 kD and the mRNA encoding pro-VIP has a molecular mass of 17.5 kD.
Linder et al. (1987) also cloned the VIP and PHM27 precursor gene, which is referred to as the VIP gene. RNA expression studies in rat detected VIP-specific probe in brain and duodenum. Expression of a VIP-encoding mRNA was observed in several areas of the rat brain including the hippocampus, cortex, colliculum, olfactory bulb, thalamus, and hypothalamus.
Linder et al. (1987) determined that the VIP gene contains 7 exons spanning approximately 9 kb. Exon 2 encodes a putative signal peptide, and exons 4 and 5 encode the PHM27 and VIP transcripts, respectively. Bodner et al. (1985) had shown that VIP and PHM-27 are encoded by adjacent exons.
By in situ hybridization techniques, Gozes et al. (1987) assigned the VIP gene to chromosome 6q24. Gotoh et al. (1988) assigned the VIP gene to chromosome 6 by spot blot hybridization of a molecularly cloned fragment of the gene to sorted chromosomes. The localization was refined to chromosome 6q26-q27 by in situ hybridization.
Heinz-Erian et al. (1985) suggested that deficient innovation of sweat glands of cystic fibrosis (219700) patients by the VIP neuropeptide might be a basic mechanism for the decreased water content and relative impermeability of the epithelium to chloride and other ions that characterize cystic fibrosis. To test this hypothesis, Gozes et al. (1987) took the 'candidate gene' approach. Gozes et al. (1987) used the PHM-27-encoding genomic fragment to detect the presence of the VIP gene at chromosome 6q21-qter. Thus, they eliminated a defective VIP gene as a candidate for the primary cause of cystic fibrosis (which is coded by chromosome 7).
Gozes et al. (1987) investigated a functional relationship between the VIP and MYB (189990) genes in neuronal tissue. They observed a sharp peak of MYB mRNA in the hippocampus of 3-day-old rats, preceding the peak of VIP mRNA that occurs in this area at 8 days of age.
Omary and Kagnoff (1987) found nuclear receptors for VIP in a human colonic adenocarcinoma cell line.
Vasoactive intestinal peptide is a neuropeptide present in the lymphoid microenvironment that elicits a broad spectrum of biologic functions, including the modulation of innate and adaptive immunity, and shows a predominant antiinflammatory action. VIP promotes TH2 differentiation and inhibits TH1 responses by regulating macrophage costimulatory signals and probably IL12/IFN-gamma production. In collagen-induced arthritis, a murine model for rheumatoid arthritis, Delgado et al. (2001) administered VIP daily or on alternate days for 2 weeks. Treatment with VIP significantly reduced incidence and severity of arthritis in this model, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of VIP was associated with downregulation of both inflammatory and autoimmune components of the disease. Delgado et al. (2001) concluded that VIP is a viable candidate for the development of treatments for rheumatoid arthritis.
Troger et al. (2001) investigated neurotransmitter behavior in the streptozotocin-induced diabetic rat retina. They found reduction of substance P (162320) and VIP, in contrast to the previously established elevations in GABA and glycine in the early stages of diabetic retinopathy. The authors stated that the reductions in substance P and VIP are noteworthy for the following reasons: first, both peptides are known to modulate excitability of inner retinal neurons; second, the reductions might be the result of excitotoxin damage; and third, the finding may help explain why retinal neovascularization does not occur in this animal model, although VEGF (192240) is massively upregulated, as substance P is a very potent vascular growth factor.
An age-related decline in macular choroidal blood flow (ChBF) occurs in humans. Because vasodilatory nerve fibers containing VIP innervate choroidal blood vessels, Jablonski et al. (2007) studied the macular choroid punches from 35 healthy human donors ranging from 21 to 93 years of age to examine the possibility that an age-related loss of these fibers might occur in the submacular choroid, and thus contribute to a decline in ChBF. Fully adjusted multivariate analysis showed a significant age-related reduction in both VIP-positive fiber abundance and diameter. VIP-positive fiber abundance showed a significant direct correlation with choroidal vessel diameter.
Mardinly et al. (2016) demonstrated that exposure of dark-housed mice to light induces a gene program in cortical Vip-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. Mardinly et al. (2016) identified Igf1 (147440) as one of several activity-regulated genes that are specific to Vip neurons, and demonstrate that Igf1 functions cell-autonomously in Vip neurons to increase inhibitory synaptic input onto these neurons. The authors concluded that their findings suggested that in cortical Vip neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of Igf1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.
Noting that VIP had been reported absent in pulmonary arteries from patients with idiopathic pulmonary arterial hypertension (PAH; 178600), Said et al. (2007) generated Vip -/- mice and examined them for evidence of PAH. Vip -/- mice exhibited moderate right ventricular (RV) hypertension, RV hypertrophy confirmed by increased ratio of RV to left ventricle plus septum weight, and an enlarged, thickened pulmonary artery and smaller branches with increased muscularization and narrowed lumens compared to wildtype mice. Lung sections also showed perivascular inflammatory cell infiltrates. There was no systemic hypertension or arterial hypoxemia to explain the PAH. The condition was associated with increased mortality. Both the vascular remodeling and RV remodeling were attenuated after a 4-week treatment with VIP. Said et al. (2007) concluded that the Vip -/- mouse was not an exact model of PAH but would be useful for studying molecular mechanisms of PAH and evaluating potential therapeutic agents.
Bodner, M., Fridkin, M., Gozes, I. Coding sequences for vasoactive intestinal peptide and PHM-27 peptide are located on two adjacent exons in the human genome. Proc. Nat. Acad. Sci. 82: 3548-3551, 1985. [PubMed: 2987932] [Full Text: https://doi.org/10.1073/pnas.82.11.3548]
Delgado, M., Abad, C., Martinez, C., Leceta, J., Gomariz, R. P. Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease. Nature Med. 7: 563-568, 2001. [PubMed: 11329057] [Full Text: https://doi.org/10.1038/87887]
Gotoh, E., Yamagami, T., Yamamoto, H., Okamoto, H. Chromosomal assignment of human VIP/PHM-27 gene to 6q26-q27 region by spot blot hybridization and in situ hybridization. Biochem. Int. 17: 555-562, 1988. [PubMed: 3202886]
Gozes, I., Avidor, R., Yahav, Y., Katznelson, D., Croce, C. M., Huebner, K. The gene encoding vasoactive intestinal peptide is located on human chromosome 6p21-6qter. Hum. Genet. 75: 41-44, 1987. [PubMed: 3026947] [Full Text: https://doi.org/10.1007/BF00273836]
Gozes, I., Nakai, H., Byers, M., Avidor, R., Weinstein, Y., Shani, Y., Shows, T. B. Sequential expression in the nervous system of C-MYB and VIP genes, located in human chromosomal region 6q24. Somat. Cell Molec. Genet. 13: 305-313, 1987. [PubMed: 2842874] [Full Text: https://doi.org/10.1007/BF01534924]
Heinz-Erian, P., Dey, R. D., Flux, M., Said, S. I. Deficient vasoactive intestinal peptide innervation in sweat glands of cystic fibrosis patients. Science 229: 1407-1408, 1985. [PubMed: 4035357] [Full Text: https://doi.org/10.1126/science.4035357]
Itoh, N., Obata, K., Yanaihara, N., Okamoto, H. Human preprovasoactive intestinal polypeptide contains a novel PHI-27-like peptide, PHM-27. Nature 304: 547-549, 1983. [PubMed: 6571696] [Full Text: https://doi.org/10.1038/304547a0]
Jablonski, M. M., Iannaccone, A., Reynolds, D. H., Gallaher, P., Allen, S., Wang, X., Reiner, A. Age-related decline in VIP-positive parasympathetic nerve fibers in the human submacular choroid. Invest. Ophthal. Vis. Sci. 48: 479-485, 2007. [PubMed: 17251439] [Full Text: https://doi.org/10.1167/iovs.06-0972]
Linder, S., Barkhem, T., Norberg, A., Persson, H., Schalling, M., Hokfelt, T., Magnusson, G. Structure and expression of the gene encoding the vasoactive intestinal peptide precursor. Proc. Nat. Acad. Sci. 84: 605-609, 1987. [PubMed: 3025882] [Full Text: https://doi.org/10.1073/pnas.84.2.605]
Mardinly, A. R., Spiegel, I., Patrizi, A., Centofante, E., Bazinet, J. E., Tzeng, C. P., Mandel-Brehm, C., Harmin, D. A., Adesnik, H., Fagiolini, M., Greenberg, M. E. Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons. Nature 531: 371-375, 2016. [PubMed: 26958833] [Full Text: https://doi.org/10.1038/nature17187]
Omary, M. B., Kagnoff, M. F. Identification of nuclear receptors for VIP on a human colonic adenocarcinoma cell line. Science 238: 1578-1581, 1987. [PubMed: 2825352] [Full Text: https://doi.org/10.1126/science.2825352]
Said, S. I., Hamidi, S. A., Dickman, K. G., Szema, A. M., Lyubsky, S., Lin, R. Z., Jiang, Y.-P., Chen, J. J., Waschek, J. A., Kort, S. Moderate pulmonary arterial hypertension in male mice lacking the vasoactive intestinal peptide gene. Circulation 115: 1260-1268, 2007. [PubMed: 17309917] [Full Text: https://doi.org/10.1161/CIRCULATIONAHA.106.681718]
Troger, J., Neyer, S., Heufler, C., Huemer, H., Schmid, E., Griesser, U., Kralinger, M., Kremser, B., Baldissera, I., Kieselbach, G. Substance P and vasoactive intestinal polypeptide in the streptozotocin-induced diabetic rat retina. Invest. Ophthal. Vis. Sci. 42: 1045-1050, 2001. [PubMed: 11274084]