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α2C-adrenoceptor

Family: Adrenoceptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 462 4p16 ADRA2C adrenoceptor alpha 2C 23
Mouse 7 458 5 B2 Adra2c adrenergic receptor, alpha 2c 17
Rat 7 458 14q21 Adra2c adrenoceptor alpha 2C 9
Previous and Unofficial Names
α2-C4
ADRA2L2
ADRA2RL2
ADRARL2
adrenergic, alpha-2C-, receptor
Adrenergic alpha2C- receptor class I
Adrenergic, alpha2C-, receptor class I
adrenergic receptor, alpha 2c
alpha-2 adrenergic receptor subtype C4
alpha-2C adrenergic receptor
alpha-2C adrenoceptor
alpha-2C adrenoreceptor
alpha-2CAR
subtype alpha2-C4
alpha2-C4
alpha2C
[a]2C
Adra-2c
Database Links
ChEMBL Target 218 (Hs), 11833 (Mm), 12216 (Rn)
DrugBank Target 378 (Hs)
Ensembl ENSG00000184160 (Hs), ENSMUSG00000045318 (Mm), ENSRNOG00000009299 (Rn)
Entrez Gene 152 (Hs), 11553 (Mm), 24175 (Rn)
GeneCards ADRA2C (Hs)
GenitoUrinary Development Molecular Anatomy Project Adra2c (Mm)
HomoloGene 20170 (Hs)
Human Protein Reference Database 00085 (Hs)
InterPro P18825 (Hs), Q01337 (Mm), P22086 (Rn)
KEGG Gene hsa:152 (Hs), mmu:11553 (Mm), rno:24175 (Rn)
OMIM 104250 (Hs)
PharmGKB Gene PA37 (Hs)
PhosphoSitePlus P18825 (Hs), Q01337 (Mm), P22086 (Rn)
Protein Ontology (PRO) PRO:000001188 (Hs)
RefSeq Nucleotide NM_000683 (Hs), NM_007418 (Mm), NM_138506 (Rn)
RefSeq Protein NP_000674 (Hs), NP_031444 (Mm), NP_612515 (Rn)
TreeFam ENSG00000184160 (Hs), ENSMUSG00000045318 (Mm), ENSRNOG00000009299 (Rn)
UniGene Hs. 123022 (Hs)
UniProt P18825 (Hs), Q01337 (Mm), P22086 (Rn)
Wikipedia α2C-adrenoceptor
Adrenoceptors
Search for 3D structures on the PDB
Search by keyword: Adrenoceptors α2C-adrenoceptor Search by accession number: P22086, P18825, Q01337
Natural/Endogenous Ligand(s)
(-)-adrenaline
(-)-noradrenaline
Comments: Adrenaline exhibits greater relative potency than noradrenaline
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
dexmedetomidine Hs Full agonist 7.0 – 9.3 pKi 13,19,21
(-)-noradrenaline Hs Full agonist 5.9 – 8.7 pKi 13,19,21
pergolide Hs Partial agonist 7.2 pKi 18
clonidine Hs Partial agonist 6.0 – 7.8 pKi 13,19,21
oxymetazoline Hs Partial agonist 6.7 pKi 13,25
brimonidine Hs Partial agonist 5.7 – 7.6 pKi 13,19,21
(±)-adrenaline Hs Full agonist 5.8 – 6.2 pKi 13
guanfacine Hs Partial agonist 5.4 – 6.2 pKi 13
xylazine Hs Partial agonist 4.8 – 5.9 pKi 13
Agonist Comments
[125I]p-iodoclonidine binds to the human α2C receptor with a Kd of 1.3 nM [22].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
JP1302 Hs Antagonist 7.8 pKB 24
[3H]MK-912 Hs Antagonist 10.1 pKd 25
[3H]rauwolscine Hs Antagonist 9.9 pKd 3-4
[3H]RX821002 Hs Antagonist 8.2 – 9.2 pKd 4-5
lisuride Hs Antagonist 9.9 pKi 18
rauwolscine Hs Antagonist 9.1 pKi 25
terguride Hs Antagonist 9.1 pKi 18
spiroxatrine Hs Antagonist 9.0 pKi 25
yohimbine Hs Antagonist 8.5 – 9.5 pKi 3,5,25
WB 4101 Hs Antagonist 8.4 – 9.4 pKi 3,5,25
roxindole Hs Antagonist 8.8 pKi 18
RX821002 Hs Antagonist 8.7 pKi 25
phentolamine Hs Antagonist 7.6 – 7.9 pKi 3,5
cabergoline Hs Antagonist 7.7 pKi 18
bromocriptine Hs Antagonist 7.6 pKi 18
ARC-239 Hs Antagonist 6.7 – 8.4 pKi 3,5,25
apomorphine Hs Antagonist 7.4 pKi 18
prazosin Hs Antagonist 6.7 – 8.0 pKi 3,5,25
piribedil Hs Antagonist 7.2 pKi 18
chlorpromazine Hs Antagonist 6.9 – 7.4 pKi 3,5
BRL 44408 Hs Antagonist 6.8 pKi 25

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

Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Potassium channel
Calcium channel
References:  2,15
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
Comments:  The physiological significance of this mechanism is unknown.
References:  8
Tissue Distribution
Brain = kidney > aorta = lung = skeletal muscle = heart = spleen.
Absent in the liver.
Species:  Human
Technique:  RNAse protection of mRNA.
References:  7,20
Brain >> kidney.
Absent in spleen, aorta, heart, liver, lung, skeletal muscle.
Species:  Human
Technique:  RNAse protection of mRNA.
References:  1,11
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
Measurment of adenylate cyclase activity. This assay is done intact cell preparations (either native or transfected) using the [3H]adenine prelabeling technique to measure cAMP accumulation.
Species:  Human
Tissue: 
Response measured:  Inhibition of cAMP accumulation.
References:  2
Isometric contraction is measured with rings of human saphenous veins (3–5 mm) attached to myograph transducers under 1 g tension in organ bath at 37 °C.
Species:  Human
Tissue:  Saphenous vein.
Response measured:  Contraction.
References:  6,10
Physiological Functions
Presynaptic inhibition of noradrenaline release.
Species:  Mouse
Tissue:  Heart; central noradrenergic neurons.
References:  12,14
Physiological Consequences of Altering Gene Expression
α2C-adrenoceptor knock-out mice show no change in cardiovascular and sedative effects with a non-selective adrenoceptor agonist.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  14
The development of α2B and α2C knock-out mice has shown that these two subtypes are not involved in the central hypotensive response to α2 agonists.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  16
α2C knockout mice exhibit disruption of presynaptic inhibition of noradrenaline release at low stimulation frequencies.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  12
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Adra2atm1Bkk|Adra2btm1Gsb|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2btm1Gsb/Adra2btm1Gsb,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87934  MGI:87935  MGI:87936  MP:0001712 abnormal placenta development PMID: 12068299 
Adra2ctm1Gsb Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87936  MP:0008428 abnormal spatial working memory PMID: 10051760  11642653 
Adra2atm1Bkk|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87934  MGI:87936  MP:0005447 abnormal synaptic norepinephrine release PMID: 10647009 
Adra2atm1Bkk|Adra2btm1Gsb|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2btm1Gsb/Adra2btm1Gsb,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87934  MGI:87935  MGI:87936  MP:0001718 abnormal yolk sac morphology PMID: 12068299 
Adra2ctm1Gsb Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87936  MP:0002573 behavioral despair PMID: 10523817 
Adra2atm1Bkk|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87934  MGI:87936  MP:0001625 cardiac hypertrophy PMID: 10647009 
Adra2atm1Bkk|Adra2btm1Gsb|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2btm1Gsb/Adra2btm1Gsb,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87934  MGI:87935  MGI:87936  MP:0005333 decreased heart rate PMID: 12068299 
Adra2atm1Bkk|Adra2btm1Gsb|Adra2ctm1Gsb Adra2atm1Bkk/Adra2atm1Bkk,Adra2btm1Gsb/Adra2btm1Gsb,Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87934  MGI:87935  MGI:87936  MP:0006207 embryonic lethality during organogenesis PMID: 12068299 
Adra2ctm1Gsb Adra2ctm1Gsb/Adra2ctm1Gsb
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J		 MGI:87936  MP:0001488 increased startle reflex PMID: 9526020 

REFERENCES

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1. Blaxall, H. S., Hass, N. A. and Bylund, D. B. (1994) Expression of α2-adrenergic receptor genes in rat tissues. Receptor, 4: 191-199. [PMID:7812219]

2. Bylund, D. B. and Ray-Prenger, C. (1989) Alpha-2A and alpha-2B adrenergic receptor subtypes: attenuation of cyclic AMP production in cell lines containing only one receptor subtype. J. Pharmacol. Exp. Ther., 251: 640-644. [PMID:2553931]

3. Bylund, D. B., Blaxall, H. S., Iversen, L. J., Caron, M. G., Lefkowitz, R. J. and Lomasney, J. W. (1992) Pharmacological characteristics of alpha 2-adrenergic receptors: comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning. Mol Pharmacol., 42: 1-5. [PMID:1353247]

4. Deupree, J. D., Hinton, K. A., Cerutis, D. R. and Bylund, D. B. (1996) Buffers differentially alter the binding of [3H]rauwolscine and [3H]RX821002 to the alpha-2 adrenergic receptor subtypes. J Pharmacol Exp Ther., 278: 1215-1227. [PMID:8819505]

5. Devedjian, J. C., Esclapez, F., Denis-Pouxviel, C. and Paris, H. (1994) Further characterization of human alpha 2-adrenoceptor subtypes: [3H]RX821002 binding and definition of additional selective drugs. Eur J Pharmacol., 252: 43-49. [PMID:7908642]

6. Docherty, J. R. (1998) Subtypes of functional alpha-1 and alpha-2 adrenoceptors. Eur J Pharmacol., 361: 1-15. [PMID:9851536]

7. Eason, M. G. and Liggett, S. B. (1993) Human alpha-2 adrenergic receptor subtype distribution: Widespread and subtype-selective expression of alpha 2C10, alpha 2C4, and alpha 2C2 mRNA in multiple tissues. Mol Pharmacol., 44: 70-75. [PMID:7688069]

8. Eason, M. G., Kurose, H., Holt, B. D., Raymond, J. R. and Liggett, S. B. (1992) Simultaneous coupling of alpha 2-adrenergic receptors to two G-proteins with opposing effects. Subtype-selective coupling of alpha 2C10, alpha 2C4, and alpha 2C2 adrenergic receptors to Gi and Gs. J Biol Chem., 267: 15795-15801. [PMID:1322406]

9. Flordellis, C. S., Handy, D. E., Bresnahan, M. R., Zannis, V. I. and Gavras, H. (1991) Cloning and expression of a rat brain alpha 2B-adrenergic receptor. Proc Natl Acad Sci USA., 88: 1019-1023. [PMID:1704126]

10. Gavin, K. T., Colgan, M. P., Moore, D., Shanik, G. and Docherty, J. R. (1997) α2C-adrenoceptors mediate contractile responses to noradrenaline in the human saphenous vein. Naunyn Schmiedebergs Arch. Pharmacol., 355: 406-411. [PMID:9089673]

11. Handy, D. E., Flordellis, C. S., Bogdanova, N. N., Bresnahan, M. R. and Gavras, H. (1993) Diverse tissue expression of rat alpha 2-adrenergic receptor genes. Hypertension., 21: 861-865. [PMID:7684725]

12. Hein, L., Altman, J. D. and Kobilka, B. K. (1999) Two functionally distinct 2-adrenergic receptors regulate sympathetic neurotransmission. Nature., 402: 181-118. [PMID:10647009]

13. Jasper, J. R., Lesnick, J. D., Chang, L. K., Yamanishi, S. S., Chang, T. K., Hsu, S. A. O., Daunt, D. A., Bonhaus, D. W. and Eglen, R. M. (1998) Ligand efficacy and potency at recombinant alpha 2 adrenergic receptors - Agonist-mediated [35S]GTPgammaS binding. Biochem Pharmacol., 55: 1035-1043. [PMID:9605427]

14. Kable, J. W., Murrin, L. C. and Bylund, D. B. (2000) In vivo gene modification elucidates subtype-specific functions of alpha-2 adrenergic receptors. J Pharmacol Exp Ther., 293: 1-7. [PMID:10734146]

15. Limbird, L. E. (1988) Receptors linked to inhibition of adenylate cyclase: Additional signaling mechanisms. FASEB J., 2: 2686-2695. [PMID:2840317]

16. Link, R. E., Desai, K., Hein, L., Stevens, M. E., Chruscinski, A., Bernstein, D., Barsh, G. S. and Kobilka, B. K. (1996) Cardiovascular regulation in mice lacking alpha-2 adrenergic receptor subtypes B and C. Science., 273: 803-805. [PMID:8670422]

17. Link, R., Daunt, D., Barsh, G., Chruscinski, A. and Kobilka, B. (1992) Cloning of two mouse genes encoding alpha 2-adrenergic receptor subtypes and identification of a single amino acid in the mouse alpha 2-C10 homolog responsible for an interspecies variation in antagonist binding. Mol Pharmacol., 42: 16-27. [PMID:1353249]

18. Millan, M. J., Maiofiss, L., Cussac, D., Audinot, V., Boutin, J. A. and Newman-Tancredi, A. (2002) Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes. J Pharmacol Exp Ther, 303: 791-804. [PMID:12388666]

19. Peltonen, J. M., Pihlavisto, M. and Scheinin, M. (1998) Subtype-specific stimulation of [35S]GTPgammaS binding by recombinant alpha-2 adrenoceptors. Eur J Pharmacol., 355: 275-279. [PMID:9760042]

20. Perala, M., Hirvonen, H., Kalimo, H., Ala-Uotila, S., Regan, J. W., Akerman, K. E. and Scheinin, M. (1992) Differential expression of two alpha 2-adrenergic receptor subtype mRNAs in human tissues. Mol Brain Res., 16: 57-63. [PMID:1334200]

21. Pihlavisto, M., Sjöholm, B., Scheinin, M. and Wurster, S. (1998) Modulation of agonist binding to recombinant human alpha-2 adrenoceptors by sodium ions. Biochim Biophys Acta Mol Cell Res., 1448: 135-146. [PMID:9824686]

22. Piletz, J. E., Zhu, H. and Chikkala, D. N. (1996) Comparison of ligand binding affinities at human I1-imidazoline binding sites and the high affinity state of alpha-2 adrenoceptor subtypes. J. Pharmacol. Exp. Ther., 279: 694-702. [PMID:8930173]

23. Regan, J. W., Kobilka, T. S., Yang-Feng, T. L., Caron, M. G., Lefkowitz, R. J. and Kobilka, B. K. (1988) Cloning and expression of a human kidney cDNA for an α2- adrenergic receptor subtype. Proc. Natl. Acad. Sci. U.S.A., 85: 6301-6305. [PMID:2842764]

24. Sallinen, J; Höglund, I; Engström, M; Lehtimäki, J; Virtanen, R; Sirviö, J; Wurster, S; Savola, JM; Haapalinna, A. (2007) Pharmacological characterization and CNS effects of a novel highly selective alpha2C-adrenoceptor antagonist JP-1302. Br. J. Pharmacol., 150 (4): 391-402. [PMID:17220913]

25. Uhlén, S., Porter, A. C. and Neubig, R. R. (1994) The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors. J Pharmacol Exp Ther, 271: 1558-1565. [PMID:7996470]

To cite this database page, please use the following:

Richard A. Bond, David B. Bylund, Douglas C. Eikenburg, J. Paul Hieble, Rebecca Hills, Kenneth P. Minneman, Sergio Parra.
Adrenoceptors: α2C-adrenoceptor. Last modified on 19/02/2013. Accessed on 22/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=27.


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