VIPR1 explained

Vasoactive intestinal polypeptide receptor 1 also known as VPAC₁, is a protein, that in humans is encoded by the VIPR1 gene. VPAC₁ is expressed in the brain (cerebral cortex, hippocampus, amygdala), lung, prostate, peripheral blood leukocytes, liver, small intestine, heart, spleen, placenta, kidney, thymus and testis.^{[1] [2] [3]}

Function

VPAC₁ is a receptor for vasoactive intestinal peptide (VIP), a small neuropeptide. Vasoactive intestinal peptide is involved in smooth muscle relaxation, exocrine and endocrine secretion, and water and ion flux in lung and intestinal epithelia. Its actions are effected through integral membrane receptors associated with a guanine nucleotide binding protein which activates adenylate cyclase.^[4]

VIP acts in an autocrine fashion via VPAC₁1 to inhibit megakaryocyte proliferation and induce proplatelet formation.^{[5] [6]}

Clinical significance

Patients with idiopathic achalasia show a significant difference in the distribution of SNPs affecting VIPR1.^[7]

VIP and PACAP levels were decreased in anterior vaginal wall of stress urinary incontinence and pelvic organ prolapse patients, they may participate in the pathophysiology of these diseases.^[8]

See also

• Vasoactive intestinal peptide receptor

Further reading

• [Quaternary structure of rabbit skeletal muscle glycogen synthetase] . Doklady Akademii Nauk SSSR . 222 . 4 . 997–1000 . Jun 1975 . 807467 . Quaternary structure of rabbit skeletal muscle glycogen synthetase .
• Sreedharan SP, Huang JX, Cheung MC, Goetzl EJ . Structure, expression, and chromosomal localization of the type I human vasoactive intestinal peptide receptor gene . Proceedings of the National Academy of Sciences of the United States of America . 92 . 7 . 2939–43 . Mar 1995 . 7708752 . 42334 . 10.1073/pnas.92.7.2939 . 1995PNAS...92.2939S . free .
• Couvineau A, Gaudin P, Maoret JJ, Rouyer-Fessard C, Nicole P, Laburthe M . Highly conserved aspartate 68, tryptophane 73 and glycine 109 in the N-terminal extracellular domain of the human VIP receptor are essential for its ability to bind VIP . Biochemical and Biophysical Research Communications . 206 . 1 . 246–52 . Jan 1995 . 7818527 . 10.1006/bbrc.1995.1034 .
• Gagnon AW, Aiyar N, Elshourbagy NA . Molecular cloning and functional characterization of a human liver vasoactive intestinal peptide receptor . Cellular Signalling . 6 . 3 . 321–33 . Mar 1994 . 7917790 . 10.1016/0898-6568(94)90037-X .
• Sreedharan SP, Patel DR, Xia M, Ichikawa S, Goetzl EJ . Human vasoactive intestinal peptide1 receptors expressed by stable transfectants couple to two distinct signaling pathways . Biochemical and Biophysical Research Communications . 203 . 1 . 141–8 . Aug 1994 . 8074647 . 10.1006/bbrc.1994.2160 .
• Couvineau A, Rouyer-Fessard C, Darmoul D, Maoret JJ, Carrero I, Ogier-Denis E, Laburthe M . Human intestinal VIP receptor: cloning and functional expression of two cDNA encoding proteins with different N-terminal domains . Biochemical and Biophysical Research Communications . 200 . 2 . 769–76 . Apr 1994 . 8179610 . 10.1006/bbrc.1994.1517 .
• Moody TW, Zia F, Draoui M, Brenneman DE, Fridkin M, Davidson A, Gozes I . A vasoactive intestinal peptide antagonist inhibits non-small cell lung cancer growth . Proceedings of the National Academy of Sciences of the United States of America . 90 . 10 . 4345–9 . May 1993 . 8389448 . 46507 . 10.1073/pnas.90.10.4345 . 1993PNAS...90.4345M . free .
• Sreedharan SP, Patel DR, Huang JX, Goetzl EJ . Cloning and functional expression of a human neuroendocrine vasoactive intestinal peptide receptor . Biochemical and Biophysical Research Communications . 193 . 2 . 546–53 . Jun 1993 . 8390245 . 10.1006/bbrc.1993.1658 .
• Couvineau A, Fabre C, Gaudin P, Maoret JJ, Laburthe M . Mutagenesis of N-glycosylation sites in the human vasoactive intestinal peptide 1 receptor. Evidence that asparagine 58 or 69 is crucial for correct delivery of the receptor to plasma membrane . Biochemistry . 35 . 6 . 1745–52 . Feb 1996 . 8639654 . 10.1021/bi952022h .
• Pozo D, Guerrero JM, Segura JJ, Calvo JR . Thymosin alpha 1 interacts with the VIP receptor-effector system in rat and mouse immunocompetent cells . Immunopharmacology . 34 . 2–3 . 113–23 . Sep 1996 . 8886855 . 10.1016/0162-3109(96)00131-2 .
• Couvineau A, Maoret JJ, Rouyer-Fessard C, Carrero I, Laburthe M . Cloning and functional characterization of the human VIP1/PACAP receptor promoter . Annals of the New York Academy of Sciences . 865 . 59–63 . Dec 1998 . 1 . 9927997 . 10.1111/j.1749-6632.1998.tb11163.x . 1998NYASA.865...59C . 46520267 .
• Knudsen SM, Tams JW, Wulff BS, Fahrenkrug J . Importance of conserved cysteines in the extracellular loops of human PACAP/VIP1 receptor for ligand binding and stimulation of cAMP production . Annals of the New York Academy of Sciences . 865 . 259–65 . Dec 1998 . 1 . 9928020 . 10.1111/j.1749-6632.1998.tb11186.x . 1998NYASA.865..259K . 27000806 .
• Marie J, Wakkach A, Coudray A, Chastre E, Berrih-Aknin S, Gespach C . Functional expression of receptors for calcitonin gene-related peptide, calcitonin, and vasoactive intestinal peptide in the human thymus and thymomas from myasthenia gravis patients . Journal of Immunology . 162 . 4 . 2103–12 . Feb 1999 . 10.4049/jimmunol.162.4.2103 . 9973484 . free .
• Mimuro H, Suzuki T, Suetsugu S, Miki H, Takenawa T, Sasakawa C . Profilin is required for sustaining efficient intra- and intercellular spreading of Shigella flexneri . The Journal of Biological Chemistry . 275 . 37 . 28893–901 . Sep 2000 . 10867004 . 10.1074/jbc.M003882200 . free .
• Nicole P, Maoret JJ, Couvineau A, Momany FA, Laburthe M . Tryptophan 67 in the human VPAC(1) receptor: crucial role for VIP binding . Biochemical and Biophysical Research Communications . 276 . 2 . 654–9 . Sep 2000 . 11027527 . 10.1006/bbrc.2000.3375 .
• Bajo AM, Juarranz MG, Valenzuela P, Martínez P, Prieto JC, Guijarro LG . Expression of vasoactive intestinal peptide (VIP) receptors in human uterus . Peptides . 21 . 9 . 1383–8 . Sep 2000 . 11072126 . 10.1016/S0196-9781(00)00282-5 . 429907 .
• Lara-Marquez M, O'Dorisio M, O'Dorisio T, Shah M, Karacay B . Selective gene expression and activation-dependent regulation of vasoactive intestinal peptide receptor type 1 and type 2 in human T cells . Journal of Immunology . 166 . 4 . 2522–30 . Feb 2001 . 11160313 . 10.4049/jimmunol.166.4.2522 . free .
• Martin Shreeve S . Identification of G-proteins coupling to the vasoactive intestinal peptide receptor VPAC(1) using immunoaffinity chromatography: evidence for precoupling . Biochemical and Biophysical Research Communications . 290 . 4 . 1300–7 . Feb 2002 . 11812005 . 10.1006/bbrc.2002.6342 .
• Dorsam G, Goetzl EJ . Vasoactive intestinal peptide receptor-1 (VPAC-1) is a novel gene target of the hemolymphopoietic transcription factor Ikaros . The Journal of Biological Chemistry . 277 . 16 . 13488–93 . Apr 2002 . 11812772 . 10.1074/jbc.M107922200 . free .
• Branch DR, Valenta LJ, Yousefi S, Sakac D, Singla R, Bali M, Sahai BM, Ma XZ . VPAC1 is a cellular neuroendocrine receptor expressed on T cells that actively facilitates productive HIV-1 infection . AIDS . 16 . 3 . 309–19 . Feb 2002 . 11834941 . 10.1097/00002030-200202150-00001 . 25584856 . free .

Notes and References

1. Ishihara T, Shigemoto R, Mori K, Takahashi K, Nagata S . Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide . Neuron . 8 . 4 . 811–9 . Apr 1992 . 1314625 . 10.1016/0896-6273(92)90101-I . 43589458 .
2. Usdin TB, Bonner TI, Mezey E . Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions . Endocrinology . 135 . 6 . 2662–80 . Dec 1994 . 7988457 . 10.1210/endo.135.6.7988457 .
3. Sreedharan SP, Huang JX, Cheung MC, Goetzl EJ . Structure, expression, and chromosomal localization of the type I human vasoactive intestinal peptide receptor gene . Proceedings of the National Academy of Sciences of the United States of America . 92 . 7 . 2939–43 . Mar 1995 . 7708752 . 42334 . 10.1073/pnas.92.7.2939 . 1995PNAS...92.2939S . free .
4. Web site: Entrez Gene: VIPR1 vasoactive intestinal peptide receptor 1.
5. Nam C, Case AJ, Hostager BS, O'Dorisio MS . The role of vasoactive intestinal peptide (VIP) in megakaryocyte proliferation . Journal of Molecular Neuroscience . 37 . 2 . 160–7 . Feb 2009 . 18663606 . 10.1007/s12031-008-9119-x . 2030939 .
6. Freson K, Peeters K, De Vos R, Wittevrongel C, Thys C, Hoylaerts MF, Vermylen J, Van Geet C . PACAP and its receptor VPAC1 regulate megakaryocyte maturation: therapeutic implications . Blood . 111 . 4 . 1885–93 . Feb 2008 . 18000164 . 10.1182/blood-2007-06-098558 . 24342247 .
7. Paladini F, Cocco E, Cascino I, Belfiore F, Badiali D, Piretta L, Alghisi F, Anzini F, Fiorillo MT, Corazziari E, Sorrentino R . Age-dependent association of idiopathic achalasia with vasoactive intestinal peptide receptor 1 gene . Neurogastroenterology and Motility . 21 . 6 . 597–602 . Jun 2009 . 19309439 . 10.1111/j.1365-2982.2009.01284.x . 24081228 .
8. Hong X, Huang L, Song Y . Role of vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide in the vaginal wall of women with stress urinary incontinence and pelvic organ prolapse . International Urogynecology Journal and Pelvic Floor Dysfunction . 19 . 8 . 1151–7 . Aug 2008 . 18351280 . 10.1007/s00192-008-0585-z . 2482642 .