Urotensin-II receptor
Ensembl | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 17: 82.37 – 82.38 Mb | Chr 11: 121.05 – 121.05 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
The urotensin-2 receptor (UR-II-R) also known as GPR14 is a class A rhodopsin family G protein coupled-receptor (GPCR) that is 386 amino acids long which binds primarily to the
Ligands
There are two known endogenous agonists for the urotensin II receptor. One is urotensin II whose mRNA is found in a variety of tissues including the brain and also blood vessels. It is a potent vasoconstrictor and can increase REM cycles. The other is
Cellular Pathway
Urotensin II Receptor interacts with the G Protein whose alpha subunit is Gαq11 which is mainly involved in activating Protein Kinase C (PKC). This then activates phospholipase C which increases the intercellular amount of calcium through the activation of IP3 which is an intracellular molecule that acts as secondary messenger. IP3 will then release calcium which then activates PKC.
When the urotensin II receptor is activated it also promotes beta arrestin translocation. Beta arrestin is important for ceasing the response of a receptor to a stimuli. Beta arrestin also brings with it other proteins that internalize the receptor which also helps in desensitizing the cell to the stimuli.[6]
Tissue distribution
Based on
Urotensin II receptors have also been found in other peripheral tissues and blood vessels. This suggests some effects on the cardiovascular system.
Function
CNS
When the urotensin II receptor is activated through an
REM sleep is controlled by the cholinergic neurons in the PPT and LDT. Local injection of urotensin II into the PPT to leads to increased REM sleep episodes where the firing of the cholinergic neurons was observed through
Cardiovascular
Short term effects of the activation of the urotensin II receptor is the burst intercellular calcium in the aorta which causes vasoconstriction of the vessel. There is also evidence that there are long term effects of the activation of the urotensin II receptor which could play a role in cardiomyocytic hypertrophy.[11]
Gene
Human urotensin II receptor is located on chromosome 17q25 as an intronless gene. There are no known subtypes of the receptor but the possibility cannot be discounted. It has similar domain sequences to the somatostatin receptor, and in lab conditions can be activated by somatostatin.[12]
Clinical significance
Mutations
There is one single-nucleotide polymorphism that is known to occur in humans regarding the urotensin II receptor. R1483.50 is instead H1483.50 which effects how the cell responds when the urotensin II receptor is activated. The receptor cannot activate the PKC but it can still activate the ERK1/2 pathway although it is a little bit slower.
There have been studies done on specific amino acids on the urotensin II receptor especially the ones that are homologous to the other members of the rhodopsin family. These include, D972.50, E1473.49, and Y1493.50. In all cases the amino acids were converted to alanine and their effects were observed. The mutated D972.50 receptor could not activate PKC nor could it activate the ERK1/2 pathway. This meant that it affected the activation of both pathways and plays a critical role. The other two amino acids which were mutated E1473.49 and Y1493.50 still activated both PKC and ERK1/2 suggesting that they did not play a critical role in the activation of the pathway.[13]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000181408 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000039321 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 2011410.
- S2CID 4564765.
- S2CID 22774771.
- S2CID 29248060.
- PMID 12885791.
- S2CID 83184639.
- PMID 11020490.
- S2CID 41304445.
- S2CID 9019351.
Further reading
- Marchese A, Heiber M, Nguyen T, Heng HH, Saldivia VR, Cheng R, Murphy PM, Tsui LC, Shi X, Gregor P (Sep 1995). "Cloning and chromosomal mapping of three novel genes, GPR9, GPR10, and GPR14, encoding receptors related to interleukin 8, neuropeptide Y, and somatostatin receptors". Genomics. 29 (2): 335–44. PMID 8666380.
- Coulouarn Y, Lihrmann I, Jegou S, Anouar Y, Tostivint H, Beauvillain JC, Conlon JM, Bern HA, Vaudry H (Dec 1998). "Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord". Proceedings of the National Academy of Sciences of the United States of America. 95 (26): 15803–8. PMID 9861051.
- Liu Q, Pong SS, Zeng Z, Zhang Q, Howard AD, Williams DL, et al. (Dec 1999). "Identification of urotensin II as the endogenous ligand for the orphan G-protein-coupled receptor GPR14". Biochemical and Biophysical Research Communications. 266 (1): 174–8. PMID 10581185.
- Protopopov A, Kashuba V, Podowski R, Gizatullin R, Sonnhammer E, Wahlestedt C, Zabarovsky ER (2000). "Assignment of the GPR14 gene coding for the G-protein-coupled receptor 14 to human chromosome 17q25.3 by fluorescent in situ hybridization". Cytogenetics and Cell Genetics. 88 (3–4): 312–3. S2CID 39854406.
- Maguire JJ, Kuc RE, Davenport AP (Oct 2000). "Orphan-receptor ligand human urotensin II: receptor localization in human tissues and comparison of vasoconstrictor responses with endothelin-1". British Journal of Pharmacology. 131 (3): 441–6. PMID 11015293.
- Sugo T, Murakami Y, Shimomura Y, Harada M, Abe M, Ishibashi Y, Kitada C, Miyajima N, Suzuki N, Mori M, Fujino M (Oct 2003). "Identification of urotensin II-related peptide as the urotensin II-immunoreactive molecule in the rat brain". Biochemical and Biophysical Research Communications. 310 (3): 860–8. PMID 14550283.
- Birker-Robaczewska M, Boukhadra C, Studer R, Mueller C, Binkert C, Nayler O (2004). "The expression of urotensin II receptor (U2R) is up-regulated by interferon-gamma". Journal of Receptor and Signal Transduction Research. 23 (4): 289–305. S2CID 8558448.
- Bousette N, Patel L, Douglas SA, Ohlstein EH, Giaid A (Sep 2004). "Increased expression of urotensin II and its cognate receptor GPR14 in atherosclerotic lesions of the human aorta". Atherosclerosis. 176 (1): 117–23. PMID 15306183.
- Suzuki S, Wenyi Z, Hirai M, Hinokio Y, Suzuki C, Yamada T, Yoshizumi S, Suzuki M, Tanizawa Y, Matsutani A, Oka Y (Oct 2004). "Genetic variations at urotensin II and urotensin II receptor genes and risk of type 2 diabetes mellitus in Japanese". Peptides. 25 (10): 1803–8. S2CID 11783160.
- Qi JS, Minor LK, Smith C, Hu B, Yang J, Andrade-Gordon P, Damiano B (Apr 2005). "Characterization of functional urotensin II receptors in human skeletal muscle myoblasts: comparison with angiotensin II receptors". Peptides. 26 (4): 683–90. S2CID 1244919.
- Lehner U, Velić A, Schroter R, Schlatter E, Sindić A (2007). "Ligands and signaling of the G-protein-coupled receptor GPR14, expressed in human kidney cells". Cellular Physiology and Biochemistry. 20 (1–4): 181–92. PMID 17595527.
- Segain JP, Rolli-Derkinderen M, Gervois N, Raingeard de la Blétière D, Loirand G, Pacaud P (Jul 2007). "Urotensin II is a new chemotactic factor for UT receptor-expressing monocytes". Journal of Immunology. 179 (2): 901–9. PMID 17617581.
- Lehmann F, Pettersen A, Currier EA, Sherbukhin V, Olsson R, Hacksell U, Luthman K (Apr 2006). "Novel potent and efficacious nonpeptidic urotensin II receptor agonists". Journal of Medicinal Chemistry. 49 (7): 2232–40. PMID 16570919.
External links
- "Urotensin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2008-12-09.
- UTS2R+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)