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VPAC1 receptor

Family: VIP and PACAP receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Consequences of Altering Gene Expression
References
Gene and Protein Information
class B G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 457 3p22 VIPR1 vasoactive intestinal peptide receptor 1 29
Mouse 7 459 9F4 Vipr1 vasoactive intestinal peptide receptor 1 14
Rat 7 459 8 Vipr1 vasoactive intestinal peptide receptor 1 1,4
Previous and Unofficial Names
PVR2
PACAP type II
VIP1
VIP
VIP1/PACAP
VIP1
VPAC1
RDC1
HVR1
VPAC1R
VIP and PACAP receptor 1
MGC95067
RATVASREC
VASREC
PACAP type II receptor
PACAP-R-2
PACAP-R2
VIP-R-1
Vasopressive intestinal peptide receptor
pituitary adenylate cyclase-activating polypeptide type II receptor
vasoactive intestinal peptide receptor 1
vasoactive intestinal polypeptide receptor 1
VIP-R1
VIP receptor subtype 1
AV071699
Database Links
ChEMBL Target 100334 (Hs)
Ensembl ENSG00000114812 (Hs), ENSMUSG00000032528 (Mm), ENSRNOG00000042405 (Rn)
Entrez Gene 7433 (Hs), 22354 (Mm), 24875 (Rn)
GeneCards VIPR1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Vipr1 (Mm)
HomoloGene 3399 (Hs)
Human Protein Reference Database 01890 (Hs)
InterPro P32241 (Hs), P97751 (Mm), P30083 (Rn)
KEGG Gene hsa:7433 (Hs), mmu:22354 (Mm), rno:24875 (Rn)
OMIM 192321 (Hs)
PharmGKB Gene PA37313 (Hs)
PhosphoSitePlus P32241 (Hs), P97751 (Mm), P30083 (Rn)
Protein Ontology (PRO) PRO:000017300 (Hs)
RefSeq Nucleotide NM_004624 (Hs), NM_011703 (Mm), NM_012685 (Rn)
RefSeq Protein NP_004615 (Hs), NP_035833 (Mm), NP_036817 (Rn)
TreeFam ENSG00000114812 (Hs), ENSMUSG00000032528 (Mm), ENSRNOG00000042405 (Rn)
UniProt P32241 (Hs), P97751 (Mm), P30083 (Rn)
Wikipedia VPAC1 receptor
VIP and PACAP receptors
Search for 3D structures on the PDB
Search by keyword: VIP and PACAP receptors VPAC1 receptor Search by accession number: P30083, P32241, P97751
Natural/Endogenous Ligand(s)
GHRH {Sp: Human} , GHRH {Sp: Mouse} , GHRH {Sp: Rat}
PACAP-27 {Sp: Human, Mouse, Rat}
PACAP-38 {Sp: Human, Mouse, Rat}
PHI {Sp: Mouse, Rat}
PHV {Sp: Rat}
secretin {Sp: Rat} , secretin {Sp: Human} , secretin {Sp: Mouse}
VIP {Sp: Human, Mouse, Rat}
Comments: VIP, PACAP-27 and PACAP-38 are the principal endogenous agonists
Rank order of potency (Human)
VIP, PACAP-27, PACAP-38 >> GHRH, PHI, secretin
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
Ro 25-1553 Hs Full agonist - - 11-12
Ro 25-1392 Hs Full agonist - - 35
[125I]VIP Hs Agonist 9.4 pKd 26
VIP {Sp: Human, Mouse, Rat} Hs Agonist 8.5 – 9.8 pKi 7,25-26,30-31,35
PACAP-27 {Sp: Human, Mouse, Rat} Hs Agonist 8.9 pKi 7
PACAP-38 {Sp: Human, Mouse, Rat} Hs Agonist 8.2 pKi 7
[Ala11,22,28]VIP Hs Agonist 8.1 pKi 26
helodermin Hs Agonist 7.3 pKi 7
GHRH {Sp: Human} Hs Agonist 6.2 pKi 7
PHM {Sp: Human} Hs Agonist 5.7 pKi 7
Ro 25-1392 Hs Agonist 5.5 pKi 35
secretin {Sp: Pig} Hs Agonist 5.0 pKi 7
VIP {Sp: Human, Mouse, Rat} Hs Agonist 7.9 – 10.0 pEC50 5,18,23,26,35
[Ala11,22,28]VIP Hs Agonist 7.6 – 10.2 pEC50 5,26
PACAP-27 {Sp: Human, Mouse, Rat} Hs Agonist 7.6 – 9.9 pEC50 5,23
PACAP-38 {Sp: Human, Mouse, Rat} Hs Agonist 7.4 – 9.7 pEC50 5
[Lys15,Arg16,Leu27]VIP-(1–7)/GRF-(8–27)-NH2 Hs Agonist 8.3 pEC50 23
BAY 55-9837 Hs Agonist 7.0 pEC50 32
PG 99-465 Hs Agonist 5.5 – 8.1 pEC50 5
Ro 25-1553 Hs Partial agonist 6.0 pEC50 18,23
Ro 25-1392 Hs Agonist 6.0 pEC50 35
PACAP-27 {Sp: Human, Mouse, Rat} Rn Agonist 9.0 pIC50 10
[Arg16]chicken secretin Rn Agonist 9.0 pIC50 11
VIP {Sp: Human, Mouse, Rat} Rn Agonist 8.7 – 9.0 pIC50 9-11
[Lys15,Arg16,Leu27]VIP-(1–7)/GRF-(8–27)-NH2 Rn Agonist 8.7 pIC50 11
N-stearyl-[Nle17]VIP Rn Agonist 8.7 pIC50 9
VIP {Sp: Human, Mouse, Rat} Hs Agonist 8.0 – 9.3 pIC50 9-11,18,23
PHV {Sp: Rat} Rn Agonist 8.5 pIC50 10
PHI {Sp: Pig} Rn Agonist 8.5 pIC50 10
[Lys15,Arg16,Leu27]VIP-(1–7)/GRF-(8–27)-NH2 Hs Agonist 7.7 – 9.0 pIC50 11,23
N-stearyl-[Nle17]VIP Hs Agonist 8.3 pIC50 9
PACAP-27 {Sp: Human, Mouse, Rat} Hs Agonist 7.8 – 8.5 pIC50 10,23
helodermin Rn Agonist 8.1 pIC50 10
[Arg16]chicken secretin Hs Agonist 7.2 pIC50 11
PG 99-465 Hs Partial agonist 6.7 pIC50 24
Ro 25-1553 Hs Partial agonist 6.0 – 7.0 pIC50 12,18,23
secretin {Sp: Pig} Rn Agonist 6.5 pIC50 10-11
PHI {Sp: Pig} Hs Agonist 6.0 pIC50 10
helodermin Hs Agonist 6.0 pIC50 10
secretin {Sp: Pig} Hs Agonist 5.8 pIC50 10-11
PHV {Sp: Rat} Hs Agonist 5.5 pIC50 10
BAY 55-9837 Hs Agonist 5.1 pIC50 32
View species-specific agonist tables
Agonist Comments
[Ala11,22,28]VIP and [Lys15,Arg16,Leu27]VIP(1–7)/GRF(8–27)-NH2 are selective VPAC1 agonists with much lower potency at VPAC2 and PAC1 receptors.
Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
PG 97-269 Rn Antagonist 8.0 pIC50 8
PG 97-269 Hs Antagonist 7.1 – 8.7 pIC50 5,8,18
N-stearyl-[Nle17] neurotensin-(6-11)/VIP-(7-28) Hs Antagonist 7.5 pIC50 23
View species-specific antagonist tables
Antagonist Comments
PG97-269 is a selective VPAC1 antagonist with much lower potency at VPAC2 and PAC1 receptors.

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  7,20,30-31
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Gq/G11 family
G protein (identity unknown) 		Phospholipase C stimulation
Phospholipase D stimulation
Comments:  Coupling to phospholipase C has been reported to be dependent on the presence of the Receptor Activity Modifying Protein RAMP2 [2].
References:  21-22,34
Tissue Distribution
Lung > prostate > peripheral blood leukocytes = liver = brain = small intestine colon = heart = spleen > placenta = kidney = thymus = testis
Species:  Human
Technique:  Northern blotting.
References:  29
Liver (hepatocytes); gastrointestinal mucosa; lobules and ducts of the mammary gland; thyroid (follicular cells); prostate (glands); urothelium of bladder and ureter; acini of the lung; pancreatic ducts; glands of uterus; adipose tissue; kidney (glomeruli);
Species:  Human
Technique:  Radioligand binding
References:  27-28
T lymphocytes
Species:  Human
Technique:  RT-PCR
References:  3
Cerebral cortex, hippocampus, amygdala
Species:  Human
Technique:  in situ hybridisation.
References:  17,33
Mucosa throughout the gastrointestinal tract; liver; uterine glands; epithelial cells of prostate and urethra; Leydig cells of the testis; white pulp of the spleen; lymphocytes in lymph nodes; medulla of the thymus; tracheal and bronchial epithelia;
Species:  Mouse
Technique:  Radioligand binding
References:  13
Macrophages at sites of inflammation strongly express VPAC1 receptors in many animal models
Species:  Mouse
Technique:  Northern blotting.
References:  15,19
Rodent lung (epithelial cells, some vascular and non-vascular smooth muscle, macrophages)
Species:  Rat
Technique:  Immunohistochemistry.
References:  16,19
Kidney: epithelium of proximal and distal tubules; thymus, adrenal medulla, bronchial epithelium, uterine smooth muscle
Species:  Rat
Technique:  in situ hybridisation.
References:  33
Lung, intestine, heart, liver, vas deferens
Species:  Rat
Technique:  Northern blotting.
References:  17,33
Expression Datasets

Click here to show/hide data

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
CHO cells stably transfected with VPAC1 receptor cDNA.
Species:  Human
Tissue:  CHO cells.
Response measured:  cAMP formation.
References:  7,26
COS-7 cells transiently transfected with VPAC1 receptor cDNA.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  cAMP formation.
References:  25
Stimulation of cAMP production in human colon cancer cell lines (eg. HT-29).
Species:  Human
Tissue:  Colon cancer cells.
Response measured:  cAMP formation.
References:  20,31
Physiological Consequences of Altering Gene Expression
VPAC1 receptor null mice are resistant to dextran sodium sulfate-induced colitis
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  36
VPAC1 receptor null mice exhibit fetal, neonatal and postweaning death owing to failure to thrive, intestinal obstruction and hypoglycemia. Disorganized hyperproliferation of intestinal epithelial cells with mucus deposition and bowel wall thickening. Small dysmorphic islets of Langerhans. Abnormal glucose and insulin tolerance.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  6

REFERENCES

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1. Cai, Y., Xin, X., Yamada, T., Muramatsu, Y., Szpirer, C. and Matsumoto, K. (1995) Assignments of the genes for rat pituitary adenylate cyclase activating polypeptide (Adcyap1) and its receptor subtypes (Adcyap1r1, Adcyap1r2, and Adcyap1r3). Cytogenet Cell Genet, 71: 193-196. [PMID:7656595]

2. Christopoulos, A., Christopoulos, G., Morfis, M., Udawela, M., Laburthe, M., Couvineau, A., Kuwasako, K., Tilakaratne, N. and Sexton, P.M. (2003) Novel receptor partners and function of receptor activity-modifying proteins. J Biol Chem., 278: 3293-3297. [PMID:12446722]

3. Delgado, M., Martinez, C., Johnson, M. C., Gomariz, R. P. and Ganea, D. (1996) Differential expression of vasoactive intestinal peptide receptors 1 and 2 (VIP-R1 and VIP-R2) mRNA in murine lymphocytes. J Neuroimmunol, 68: 27-38. [PMID:8784257]

4. Deng, A. Y., Gu, L., Rapp, J. P., Szpirer, C. and Szpirer, J. (1994) Chromosomal assignment of 11 loci in the rat by mouse-rat somatic hybrids and linkage. Mamm Genome, 5: 712-716. [PMID:7873882]

5. Dickson, L; Aramori, I; McCulloch, J; Sharkey, J; Finlayson, K. (2006) A systematic comparison of intracellular cyclic AMP and calcium signalling highlights complexities in human VPAC/PAC receptor pharmacology. Neuropharmacology, 51 (6): 1086-98. [PMID:16930633]

6. Fabricius, D; Karacay, B; Shutt, D; Leverich, W; Schafer, B; Takle, E; Thedens, D; Khanna, G; Raikwar, S; Yang, B; et al.. (2011) Characterization of Intestinal and Pancreatic Dysfunction in VPAC1-Null Mutant Mouse. Pancreas, 40 (6): 861-71. [PMID:21697765]

7. Gaudin, P., Couvineau, A., Maoret, J. J., Rouyer-Fessard, C. and Laburthe, M. (1996) Stable expression of the recombinant human VIP1 receptor in clonal Chinese hamster ovary cells: pharmacological, functional and molecular properties. Eur J Pharmacol, 302: 207-214. [PMID:8791009]

8. Gourlet, P., De Neef, P., Cnudde, J., Waelbroeck, M. and Robberecht, P. (1997) In vitro properties of a high affinity selective antagonist of the VIP1 receptor. Peptides, 18: 1555-1560. [PMID:9437716]

9. Gourlet, P., Rathe, J., De Neef, P., Cnudde, J., Vandermeers-Piret, M.C., Waelbroeck, M. and Robberecht, P. (1998) Interaction of lipophilic VIP derivatives with recombinant VIP1/PACAP and VIP2/PACAP receptors. Eur J Pharmacol., 354: 105-111. [PMID:9726637]

10. Gourlet, P., Vandermeers, A., Van Rampelbergh, J., De Neef, P., Cnudde, J., Waelbroeck, M. and Robberecht, P. (1998) Analogues of VIP, helodermin, and PACAP discriminate between rat and human VIP1 and VIP2 receptors. Ann N Y Acad Sci, 865: 247-252. [PMID:9928018]

11. Gourlet, P., Vandermeers, A., Vertongen, P., Rathe, J., De Neef, P., Cnudde, J., Waelbroeck, M. and Robberecht, P. (1997) Development of high affinity selective VIP1 receptor agonists. Peptides, 18: 1539-1545. [PMID:9437714]

12. Gourlet, P., Vertongen, P., Vandermeers, A., Vandermeers-Piret, M. C., Rathe, J., De Neef, P., Waelbroeck, M. and Robberecht, P. (1997) The long-acting vasoactive intestinal polypeptide agonist RO 25-1553 is highly selective of the VIP2 receptor subclass. Peptides, 18: 403-408. [PMID:9145428]

13. Harmar, A. J., Sheward, W. J., Morrison, C. F., Waser, B., Gugger, M. and Reubi, J. C. (2004) Distribution of the VPAC2 receptor in peripheral tissues of the mouse. Endocrinology, 145: 1203-1210. [PMID:14617572]

14. Hashimoto, H., Nishino, A., Shintani, N., Hagihara, N., Copeland, N. G., Jenkins, N. A., Yamamoto, K., Matsuda, T., Ishihara, T., Nagata, S. and Baba, A. (1999) Genomic organization and chromosomal location of the mouse vasoactive intestinal polypeptide 1 (VPAC1) receptor. Genomics, 58: 90-93. [PMID:10331949]

15. Ichikawa, S., Goto, Y., Uchino, S., Kaltreider, H. B., Goetzl, E. J. and Sreedharan, S. P. (1996) Changes in adhesion molecule expression during distinct patterns of immune cell migration in the inflamed lung. Arch Histol Cytol, 59: 443-452. [PMID:9037381]

16. Ichikawa, S., Sreedharan, S. P., Owen, R. L. and Goetzl, E. J. (1995) Immunochemical localization of type I VIP receptor and NK-1-type substance P receptor in rat lung. Am J Physiol, 268: L584-L588. [PMID:7537460]

17. Ishihara, T., Shigemoto, R., Mori, K., Takahashi, K. and Nagata, S. (1992) Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide. Neuron, 8: 811-819. [PMID:1314625]

18. Juarranz, M. G., Van, Rampelbergh J., Gourlet, P., De, Neef P., Cnudde, J., Robberecht, P. and Waelbroeck, M. (1999) Different vasoactive intestinal polypeptide receptor domains are involved in the selective recognition of two VPAC2-selective ligands. Mol Pharmacol, 56: 1280-1287. [PMID:10570056]

19. Kaltreider, H. B., Ichikawa, S., Byrd, P. K., Ingram, D. A., Kishiyama, J. L., Sreedharan, S. P., Warnock, M. L., Beck, J. M. and Goetzl, E. J. (1997) Upregulation of neuropeptides and neuropeptide receptors in a murine model of immune inflammation in lung parenchyma. Am J Respir Cell Mol Biol, 16: 133-144. [PMID:9032120]

20. Laburthe, M., Rousset, M., Boissard, C., Chevalier, G., Zweibaum, A. and Rosselin, G. (1978) Vasoactive intestinal peptide: a potent stimulator of adenosine 3':5'- cyclic monophosphate accumulation in gut carcinoma cell lines in culture. Proc Natl Acad Sci USA, 75: 2772-2775. [PMID:208077]

21. MacKenzie, C. J., Lutz, E. M., McCulloch, D. A., Mitchell, R. and Harmar, A. J. (1996) Phospholipase C activation by VIP1 and VIP2 receptors expressed in COS 7 cells involves a pertussis toxin-sensitive mechanism. Ann N Y Acad Sci, 805: 579-584. [PMID:8993443]

22. McCulloch, D. A., Lutz, E. M., Johnson, M. S., Robertson, D. N., MacKenzie, C. J., Holland, P. J. and Mitchell, R. (2001) ADP-ribosylation factor-dependent phospholipase D activation by VPAC receptors and a PAC1 receptor splice variant. Mol Pharmacol, 59: 1523-1532. [PMID:11353814]

23. Moody, T.W., Jensen, R.T., Fridkin, M. and Gozes, I. (2002) (N-stearyl, norleucine17)VIPhybrid is a broad spectrum vasoactive intestinal peptide receptor antagonist. J Mol Neurosci., 18: 29-35. [PMID:11931347]

24. Moreno, D., Gourlet, P., De, Neef P., Cnudde, J., Waelbroeck, M. and Robberecht, P. (2000) Development of selective agonists and antagonists for the human vasoactive intestinal polypeptide VPAC2 receptor. Peptides, 21: 1543-1549. [PMID:11068102]

25. Nicole, P., Du, K., Couvineau, A. and Laburthe, M. (1998) 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: 744-750. [PMID:9454823]

26. Nicole, P., Lins, L., Rouyer-Fessard, C., Drouot, C., Fulcrand, P., Thomas, A., Couvineau, A., Martinez, J., Brasseur, R. and Laburthe, M. (2000) 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: 24003-24012. [PMID:10801840]

27. Reubi, J. C. (2000) In vitro evaluation of VIP/PACAP receptors in healthy and diseased human tissues. Clinical implications. Ann N Y Acad Sci, 921: 1-25. [PMID:11193811]

28. Reubi, J. C., Laderach, U., Waser, B., Gebbers, J. O., Robberecht, P. and Laissue, J. A. (2000) Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin. Cancer Res, 60: 3105-3112. [PMID:10850463]

29. Sreedharan, S. P., Huang, J. X., Cheung, M. C. and Goetzl, E. J. (1995) Structure, expression, and chromosomal localization of the type I human vasoactive intestinal peptide receptor gene. Proc Natl Acad Sci U S A, 92: 2939-2943. [PMID:7708752]

30. Sreedharan, S. P., Patel, D. R., Huang, J. X. and Goetzl, E. J. (1993) Cloning and functional expression of a human neuroendocrine vasoactive intestinal peptide receptor. Biochem Biophys Res Commun, 193: 546-553. [PMID:8390245]

31. Sreedharan, S. P., Patel, D. R., Xia, M., Ichikawa, S. and Goetzl, E. J. (1994) Human vasoactive intestinal peptide1 receptors expressed by stable transfectants couple to two distinct signaling pathways. Biochem Biophys Res Commun, 203: 141-148. [PMID:8074647]

32. Tsutsumi, M., Claus, T. H., Liang, Y., Li, Y., Yang, L., Zhu, J., Dela Cruz, F., Peng, X., Chen, H., Yung, S. L., Hamren, S., Livingston, J. N. and Pan, C. Q. (2002) A potent and highly selective VPAC2 agonist enhances glucose-induced insulin release and glucose disposal: a potential therapy for type 2 diabetes. Diabetes, 51: 1453-1460. [PMID:11978642]

33. Usdin, T. B., Bonner, T. I. and Mezey, E. (1994) Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions. Endocrinology, 135: 2662-2680. [PMID:7988457]

34. Van Rampelbergh, J., Poloczek, P., Francoys, I., Delporte, C., Winand, J., Robberecht, P. and Waelbroeck, M. (1997) The pituitary adenylate cyclase activating polypeptide (PACAP I) and VIP (PACAP II VIP1) receptors stimulate inositol phosphate synthesis in transfected CHO cells through interaction with different G proteins. Biochim Biophys Acta, 1357: 249-255. [PMID:9223629]

35. Xia, M., Sreedharan, S. P., Bolin, D. R., Gaufo, G. O. and Goetzl, E. J. (1997) Novel cyclic peptide agonist of high potency and selectivity for the type II vasoactive intestinal peptide receptor. J Pharmacol Exp Ther, 281: 629-633. [PMID:9152366]

36. Yadav, M; Huang, MC; Goetzl, EJ. (2011) VPAC1 (vasoactive intestinal peptide (VIP) receptor type 1) G protein-coupled receptor mediation of VIP enhancement of murine experimental colitis. Cell. Immunol., 267 (2): 124-32. [PMID:21295288]

To cite this database page, please use the following:

Anthony Harmar, Jan Fahrenkrug, Edward J. Goetzl, Illana Gozes, Marc Laburthe, Victor May, Joseph R. Pisegna, Sami I. Said, David Vaudry, Hubert Vaudry, James A. Waschek.
VIP and PACAP receptors: VPAC1 receptor. Last modified on 09/01/2013. Accessed on 18/06/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=371.


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