WordNet
- the 1st letter of the Roman alphabet (同)a
- the blood group whose red cells carry the A antigen (同)type_A, group A
- a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
- (biochemistry) a nucleoside that is a structural component of nucleic acids; it is present in all living cells in a combined form as a constituent of DNA and RNA and ADP and ATP and AMP
PrepTutorEJDIC
- answer / ampere
- =sense organ / 受信装置
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2015/03/11 19:45:57」(JST)
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Adenosine A3 receptor |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
1OEA, 1R7N
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Identifiers |
Symbols |
ADORA3 ; A3AR; AD026; bA552M11.5 |
External IDs |
OMIM: 600445 MGI: 104847 HomoloGene: 550 IUPHAR: A3 ChEMBL: 256 GeneCards: ADORA3 Gene |
Gene ontology |
Molecular function |
• G-protein coupled adenosine receptor activity
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Cellular component |
• plasma membrane
• integral component of plasma membrane
• integral component of membrane
• mast cell granule
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Biological process |
• adenosine receptor signaling pathway
• histamine secretion by mast cell
• positive regulation of leukocyte migration
• inflammatory response
• signal transduction
• activation of adenylate cyclase activity
• regulation of heart contraction
• response to wounding
• positive regulation of phosphatidylinositol 3-kinase signaling
• positive regulation of mast cell degranulation
• positive regulation of inflammatory response
• positive regulation of calcium-mediated signaling
• positive regulation of mucus secretion
|
Sources: Amigo / QuickGO |
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RNA expression pattern |
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More reference expression data |
Orthologs |
Species |
Human |
Mouse |
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Entrez |
140 |
11542 |
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Ensembl |
ENSG00000121933 |
ENSMUSG00000000562 |
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UniProt |
P33765 |
Q3U4C5 |
|
RefSeq (mRNA) |
NM_000677 |
NM_001174169 |
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RefSeq (protein) |
NP_000668 |
NP_001167640 |
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Location (UCSC) |
Chr 1:
111.48 – 111.56 Mb |
Chr 3:
105.87 – 105.91 Mb |
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PubMed search |
[1] |
[2] |
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The adenosine A3 receptor, also known as ADORA3, is an adenosine receptor, but also denotes the human gene encoding it.
Contents
- 1 Function
- 2 Gene
- 3 Therapeutic implications
- 4 Selective Ligands
- 4.1 Agonists/Positive Allosteric Modulators
- 4.2 Antagonists/Negative Allosteric Modulators
- 4.3 Inverse Agonists
- 5 References
- 6 Further reading
- 7 External links
§Function
Adenosine A3 receptors are G protein-coupled receptors that couple to Gi/Gq and are involved in a variety of intracellular signaling pathways and physiological functions. It mediates a sustained cardioprotective function during cardiac ischemia, it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury, it has been implicated in both neuroprotective and neurodegenerative effects, and it may also mediate both cell proliferation and cell death. Recent publications demonstrate that adenosine A3 receptor antagonists (SSR161421) could have therapeutic potencial in bronchial asthma (17,18).
§Gene
Multiple transcript variants encoding different isoforms have been found for this gene.[1]
§Therapeutic implications
An adenosine A3 receptor agonist (CF-101) is in clinical trials for the treatment of rheumatoid arthritis.[2] In a mouse model of infarction the A3 selective agonist CP-532,903 protected against myocardial ischemia and reperfusion injury.[3]
§Selective Ligands
A number of selective A3 ligands are available.[4][5][6][7][8][9][10][11][12][13][14][15]
§Agonists/Positive Allosteric Modulators
- 2-(1-Hexynyl)-N-methyladenosine
- CF-101 (IB-MECA)
- CF-102
- 2-Cl-IB-MECA
- CP-532,903
- Inosine[16]
- LUF-6000
- MRS-3558
§Antagonists/Negative Allosteric Modulators
- KF-26777
- MRS-545
- MRS-1191
- MRS-1220
- MRS-1334
- MRS-1523
- MRS-3777
- MRE-3005-F20
- MRE-3008-F20
- PSB-11
- OT-7999
- VUF-5574
- SSR161421[17][18]
§Inverse Agonists
§References
- ^ "Entrez Gene: ADORA3 adenosine A3 receptor".
- ^ Silverman MH, Strand V, Markovits D, Nahir M, Reitblat T, Molad Y, Rosner I, Rozenbaum M, Mader R, Adawi M, Caspi D, Tishler M, Langevitz P, Rubinow A, Friedman J, Green L, Tanay A, Ochaion A, Cohen S, Kerns WD, Cohn I, Fishman-Furman S, Farbstein M, Yehuda SB, Fishman P (January 2008). "Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial". J. Rheumatol. 35 (1): 41–8. PMID 18050382.
- ^ Wan TC, Ge ZD, Tampo A, Mio Y, Bienengraeber MW, Tracey WR, Gross GJ, Kwok WM, Auchampach JA (January 2008). "The A3 adenosine receptor agonist CP-532,903 protects against myocardial ischemia/reperfusion injury via the sarcolemmal ATP sensitive potassium channel". J. Pharmacol. Exp. Ther. 324 (1): 234–43. doi:10.1124/jpet.107.127480. PMC 2435594. PMID 17906066.
- ^ Jeong LS, Lee HW, Jacobson KA, Lee SK, Chun MW (2005). "Development of potent and selective human A3 adenosine receptor agonists". Nucleic Acids Symposium Series (2004) 49 (49): 31–2. doi:10.1093/nass/49.1.31. PMID 17150618.
- ^ Gao ZG, Jacobson KA (September 2007). "Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs 12 (3): 479–92. doi:10.1517/14728214.12.3.479. PMID 17874974.
- ^ Kim SK, Gao ZG, Jeong LS, Jacobson KA (December 2006). "Docking studies of agonists and antagonists suggest an activation pathway of the A3 adenosine receptor". Journal of Molecular Graphics & Modelling 25 (4): 562–77. doi:10.1016/j.jmgm.2006.05.004. PMID 16793299.
- ^ Ge ZD, Peart JN, Kreckler LM, Wan TC, Jacobson MA, Gross GJ, Auchampach JA (December 2006). "Cl-IB-MECA Reduces Ischemia/Reperfusion Injury in Mice by Activating the A3 Adenosine Receptor". The Journal of Pharmacology and Experimental Therapeutics 319 (3): 1200–10. doi:10.1124/jpet.106.111351. PMC 2430759. PMID 16985166.
- ^ Bevan N, Butchers PR, Cousins R, Coates J, Edgar EV, Morrison V, Sheehan MJ, Reeves J, Wilson DJ (June 2007). "Pharmacological characterisation and inhibitory effects of (2R,3R,4S,5R)-2-(6-amino-2-{[(1S)-2-hydroxy-1-(phenylmethyl)ethyl]amino}-9H-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydro-3,4-furandiol, a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". European Journal of Pharmacology 564 (1-3): 219–25. doi:10.1016/j.ejphar.2007.01.094. PMID 17382926.
- ^ Priego EM, Pérez-Pérez MJ, von Frijtag Drabbe Kuenzel JK, de Vries H, Ijzerman AP, Camarasa MJ, Martín-Santamaría S (January 2008). "Selective human adenosine A3 antagonists based on pyrido[2,1-f]purine-2,4-diones: novel features of hA3 antagonist binding". ChemMedChem 3 (1): 111–9. doi:10.1002/cmdc.200700173. PMID 18000937.
- ^ Jeong LS, Lee HW, Kim HO, Tosh DK, Pal S, Choi WJ, Gao ZG, Patel AR, Williams W, Jacobson KA, Kim HD (March 2008). "Structure-activity relationships of 2-chloro-N6-substituted-4'-thioadenosine-5'-N,N-dialkyluronamides as human A3 adenosine receptor antagonists". Bioorganic & Medicinal Chemistry Letters 18 (5): 1612–6. doi:10.1016/j.bmcl.2008.01.070. PMID 18255292.
- ^ Cordeaux Y, Briddon SJ, Alexander SP, Kellam B, Hill SJ (March 2008). "Agonist-occupied A3 adenosine receptors exist within heterogeneous complexes in membrane microdomains of individual living cells". The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology 22 (3): 850–60. doi:10.1096/fj.07-8180com. PMID 17959910.
- ^ Gao ZG, Jacobson KA (April 2008). "Translocation of Arrestin Induced by Human A3 Adenosine Receptor Ligands in an Engineered Cell Line: Comparison with G Protein-dependent Pathways". Pharmacological Research : the Official Journal of the Italian Pharmacological Society 57 (4): 303–11. doi:10.1016/j.phrs.2008.02.008. PMC 2409065. PMID 18424164.
- ^ Miwatashi S, Arikawa Y, Matsumoto T, Uga K, Kanzaki N, Imai YN, Ohkawa S (August 2008). "Synthesis and biological activities of 4-phenyl-5-pyridyl-1,3-thiazole derivatives as selective adenosine A3 antagonists". Chemical & Pharmaceutical Bulletin 56 (8): 1126–37. doi:10.1248/cpb.56.1126. PMID 18670113. [dead link]
- ^ Gao ZG, Ye K, Göblyös A, Ijzerman AP, Jacobson KA (2008). "Flexible modulation of agonist efficacy at the human A3 adenosine receptor by the imidazoquinoline allosteric enhancer LUF6000". BMC Pharmacology 8: 20. doi:10.1186/1471-2210-8-20. PMC 2625337. PMID 19077268.
- ^ Bar-Yehuda S, Stemmer SM, Madi L, Castel D, Ochaion A, Cohen S, Barer F, Zabutti A, Perez-Liz G, Del Valle L, Fishman P (August 2008). "The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-kappaB signal transduction pathways". International Journal of Oncology 33 (2): 287–95. PMID 18636149.
- ^ Xiaowei Jin, Rebecca K. Shepherd, Brian R. Duling, and Joel Linden. "Inosine Binds to A3 Adenosine Receptors and Stimulates Mast Cell Degranulation"
- ^ Mikus EG, Szeredi J, Boer K, Tímári G, Finet M, Aranyi P, Galzin AM (December 2012). "Evaluation of SSR161421, a novel orally active adenosine A(3) receptor antagonist on pharmacology models". Eur. J. Pharmacol. 699 (1-3): 172–179. doi:10.1016/j.ejphar.2012.11.049. PMID 23219796.
- ^ Mikus EG, Boér K, Timári G, Urbán-Szabó K, Kapui Z, Szeredi J, Gerber K, Szabó T, Bátori S, Finet M, Arányi P, Galzin AM (December 2012). "Interaction of SSR161421, a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo". Eur. J. Pharmacol. 699 (1-3): 62–66. doi:10.1016/j.ejphar.2012.11.046. PMID 23219789.
§Further reading
- Klotz KN (2001). "Adenosine receptors and their ligands". Naunyn Schmiedebergs Arch. Pharmacol. 362 (4–5): 382–91. doi:10.1007/s002100000315. PMID 11111832.
- Monitto CL, Levitt RC, DiSilvestre D, Holroyd KJ (1995). "Localization of the A3 adenosine receptor gene (ADORA3) to human chromosome 1p". Genomics 26 (3): 637–8. doi:10.1016/0888-7543(95)80194-Q. PMID 7607699.
- Salvatore CA, Jacobson MA, Taylor HE, et al. (1993). "Molecular cloning and characterization of the human A3 adenosine receptor". Proc. Natl. Acad. Sci. U.S.A. 90 (21): 10365–9. doi:10.1073/pnas.90.21.10365. PMC 47775. PMID 8234299.
- Sajjadi FG, Firestein GS (1993). "cDNA cloning and sequence analysis of the human A3 adenosine receptor". Biochim. Biophys. Acta 1179 (1): 105–7. doi:10.1016/0167-4889(93)90077-3. PMID 8399349.
- Murrison EM, Goodson SJ, Edbrooke MR, Harris CA (1996). "Cloning and characterisation of the human adenosine A3 receptor gene". FEBS Lett. 384 (3): 243–6. doi:10.1016/0014-5793(96)00324-9. PMID 8617363.
- Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Bouma MG, Jeunhomme TM, Boyle DL, et al. (1997). "Adenosine inhibits neutrophil degranulation in activated human whole blood: involvement of adenosine A2 and A3 receptors". J. Immunol. 158 (11): 5400–8. PMID 9164961.
- Atkinson MR, Townsend-Nicholson A, Nicholl JK, et al. (1998). "Cloning, characterisation and chromosomal assignment of the human adenosine A3 receptor (ADORA3) gene". Neurosci. Res. 29 (1): 73–9. doi:10.1016/S0168-0102(97)00073-4. PMID 9293494.
- Palmer TM, Harris CA, Coote J, Stiles GL (1997). "Induction of multiple effects on adenylyl cyclase regulation by chronic activation of the human A3 adenosine receptor". Mol. Pharmacol. 52 (4): 632–40. PMID 9380026.
- Liang BT, Jacobson KA (1998). "A physiological role of the adenosine A3 receptor: Sustained cardioprotection". Proc. Natl. Acad. Sci. U.S.A. 95 (12): 6995–9. doi:10.1073/pnas.95.12.6995. PMC 22715. PMID 9618527.
- Dougherty C, Barucha J, Schofield PR, et al. (1999). "Cardiac myocytes rendered ischemia resistant by expressing the human adenosine A1 or A3 receptor". FASEB J. 12 (15): 1785–92. PMID 9837869.
- Murphy WJ, Eizirik E, Johnson WE, et al. (2001). "Molecular phylogenetics and the origins of placental mammals". Nature 409 (6820): 614–8. doi:10.1038/35054550. PMID 11214319.
- Gao ZG, Chen A, Barak D, et al. (2002). "Identification by site-directed mutagenesis of residues involved in ligand recognition and activation of the human A3 adenosine receptor". J. Biol. Chem. 277 (21): 19056–63. doi:10.1074/jbc.M110960200. PMID 11891221.
- Broussas M, Cornillet-Lefèbvre P, Potron G, Nguyên P (2003). "Adenosine inhibits tissue factor expression by LPS-stimulated human monocytes: involvement of the A3 adenosine receptor". Thromb. Haemost. 88 (1): 123–30. PMID 12152652.
- Merighi S, Mirandola P, Milani D, et al. (2002). "Adenosine receptors as mediators of both cell proliferation and cell death of cultured human melanoma cells". J. Invest. Dermatol. 119 (4): 923–33. doi:10.1046/j.1523-1747.2002.00111.x. PMID 12406340.
- Trincavelli ML, Tuscano D, Marroni M, et al. (2002). "A3 adenosine receptors in human astrocytoma cells: agonist-mediated desensitization, internalization, and down-regulation". Mol. Pharmacol. 62 (6): 1373–84. doi:10.1124/mol.62.6.1373. PMID 12435805.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Feoktistov I, Ryzhov S, Goldstein AE, Biaggioni I (2003). "Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors". Circ. Res. 92 (5): 485–92. doi:10.1161/01.RES.0000061572.10929.2D. PMID 12600879.
- Gao ZG, Kim SK, Gross AS, et al. (2003). "Identification of essential residues involved in the allosteric modulation of the human A(3) adenosine receptor". Mol. Pharmacol. 63 (5): 1021–31. doi:10.1124/mol.63.5.1021. PMID 12695530.
§External links
- "Adenosine Receptors: A3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Adenosinergics
|
|
Receptor
(ligands) |
AR
|
- Agonists: 2-(1-Hexynyl)-N-methyladenosine
- 2-Cl-IB-MECA
- 2'-MeCCPA
- 4'-O-β-D-Glucosyl-9-O-(6''-deoxysaccharosyl)olivil
- 5'-N-ethylcarboxamidoadenosine
- Adenosine
- Apadenoson
- ATL-146e
- BAY 60–6583
- Binodenoson
- Capadenoson
- CCPA
- CGS-21680
- CP-532,903
- GR 79236
- LUF-5835
- LUF-5845
- N6-Cyclopentyladenosine
- Regadenoson
- SDZ WAG 994
- Selodenoson
- Sonedenoson
- Tecadenoson
- UK-432,097
- Antagonists: 8-Chlorotheophylline
- 8-Phenyl-1,3-dipropylxanthine
- 8-Phenyltheophylline
- Acefylline
- Aminophylline
- ATL-444
- Bamifylline
- Cafedrine
- Caffeine
- Caffeine citrate
- Cartazolate
- CF-101
- CGS-15943
- Choline theophyllinate
- CPX
- CVT-6883
- Dimethazan
- Dyphylline
- DPCPX
- Enprofylline
- Etazolate
- Fenethylline
- IBMX
- Isovaleric acid
- Istradefylline
- KF-26777
- MRE3008F20
- MRS-1220
- MRS-1334
- MRS-1706
- MRS-1754
- MRS-3777
- Paraxanthine
- Pentoxifylline
- Preladenant
- Propentofylline
- Proxyphylline
- PSB-10
- PSB-11
- PSB 36
- PSB-603
- PSB-788
- PSB-1115
- Rolofylline
- SCH-442,416
- SCH-58261
- Theobromine
- Theodrenaline
- Theophylline
- Tozadenant
- Tracazolate
- VUF-5574
- ZM-241,385
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Transporter
(blockers) |
ENTs
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- Barbiturates
- Benzodiazepines
- Cilostazol
- Dilazep
- Dipyridamole
- Ethanol
- Hexobendine
- NBMPR
- Pentoxifylline
- Propentofylline
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PMAT
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UpToDate Contents
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English Journal
- Fragment-Based Discovery of Subtype-Selective Adenosine Receptor Ligands from Homology Models.
- Ranganathan A1, Stoddart LA2, Hill SJ2, Carlsson J3.
- Journal of medicinal chemistry.J Med Chem.2015 Dec 24;58(24):9578-90. doi: 10.1021/acs.jmedchem.5b01120. Epub 2015 Dec 8.
- Fragment-based lead discovery (FBLD) holds great promise for drug discovery, but applications to G protein-coupled receptors (GPCRs) have been limited by a lack of sensitive screening techniques and scarce structural information. If virtual screening against homology models of GPCRs could be used to
- PMID 26592528
- Selective A3 adenosine receptor agonist protects against doxorubicin-induced cardiotoxicity.
- Galal A1, El-Bakly WM2, Al Haleem EN3, El-Demerdash E4.
- Cancer chemotherapy and pharmacology.Cancer Chemother Pharmacol.2015 Dec 16. [Epub ahead of print]
- PURPOSE: Doxorubicin (DOX) is an effective anticancer drug; however, its clinical use is limited by its cardiotoxic effect. Adenosine was proved to mediate anti-inflammatory effects and protected from myocardial ischemia/reperfusion injury. So the present work was designed to examine the effectivene
- PMID 26676227
- Stimulation of gastric acid secretion by rabbit parietal cell A2B adenosine receptor activation.
- Arin RM1, Vallejo AI2, Rueda Y2, Fresnedo O2, Ochoa B2.
- American journal of physiology. Cell physiology.Am J Physiol Cell Physiol.2015 Dec 15;309(12):C823-34. doi: 10.1152/ajpcell.00224.2015. Epub 2015 Oct 14.
- Adenosine modulates different functional activities in many cells of the gastrointestinal tract; some of them are believed to be mediated by interaction with its four G protein-coupled receptors. The renewed interest in the adenosine A2B receptor (A2BR) subtype can be traced by studies in which the
- PMID 26468208
Japanese Journal
- Impaired Inhibitory Function of Presynaptic A₁-Adenosine Receptors in SHR Mesenteric Arteries
- Rocha-Pereira Carolina,Arribas Silvia Magdalena,Fresco Paula [他],Carmen González Maria,Gonçalves Jorge,Diniz Carmen
- Journal of Pharmacological Sciences 122(2), 59-70, 2013
- … In hypertension, vascular reactivity alterations have been attributed to numerous factors, including higher sympathetic innervation/adenosine. … This study examined the modulation of adenosine receptors on vascular sympathetic nerves and their putative contribution to higher noradrenaline spillover in hypertension. …
- NAID 130003362703
- Surface plasmon resonance-biosensor detects the diversity of responses against epidermal growth factor in various carcinoma cell lines
- Hiragun Takaaki,Yanase Yuhki,Kose Kazuhiro,Kawaguchi Tomoko,Uchida Kazue,Tanaka Shinji,Hide Michihiro
- Biosensors & Bioelectronics 32(1), 202-207, 2012
- … We previously reported that the activation of epidermal growth factor receptor (EGFR) on keratinocytes causes a unique triphasic change of AR, whereas the activation of other receptors, such as IgE receptor and adenosine A3 receptor on mast cells, causes a transient monophasic increase of AR. …
- NAID 120005308252
- A New Series of 2-Alkoxy(aralkoxy)-[1,2,4]triazolo[1,5-a]quinazolin-5-ones as Adenosine Receptor Antagonists
- Al-Salahi Rashad,Geffken Detlef,Koellner Maria
- Chemical and Pharmaceutical Bulletin 59(6), 730-733, 2011
- … This research was carried out to study the pharmacological activity of a newly synthesized series of 2-alkoxy-[1,2,4]triazolo[1,5-a]quinazolin-5-ones as adenosine receptor antagonists. … These compounds have been tested in radioligand binding assays on cloned Chinese hamster ovary (CHO) cells transfected with A1, A2A, A2B and A3 receptors. …
- NAID 130000747998
Related Links
- Data show that A2A and A3 adenosine receptor density inversely correlated with Disease Activity Score in 28 or 44 joints (DAS28 or DAS) suggesting a direct role of the endogenous activation of these receptors in the control of ...
- GoPubMed lists recent and important papers and reviews for adenosine A3 receptor(adenosine A3 receptor) ... This gene encodes a protein that belongs to the family of adenosine receptors, which are G-protein-coupled receptors that ...
Related Pictures
★リンクテーブル★
[★]
- 英
- adenosine A3 receptor
- 関
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[★]
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- adenosine A3 receptor
- 関
- アデノシンA3受容体
[★]