Biology:Alpha-1A adrenergic receptor
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
The alpha-1A adrenergic receptor (α1A adrenoreceptor), also known as ADRA1A, formerly known also as the alpha-1C adrenergic receptor,[1] is an alpha-1 adrenergic receptor, and also denotes the human gene encoding it.[2] There is no longer a subtype α1C receptor. At one time, there was a subtype known as α1C, but it was found to be identical to the previously discovered α1A receptor subtype. To avoid confusion, the naming convention was continued with the letter D.
Receptor
There are 3 alpha-1 adrenergic receptor subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 family of G-proteins. Different subtypes show different patterns of activation. The majority of alpha-1 receptors are directed toward the function of epinephrine, a hormone that has to do with the fight-or-flight response.
Gene
This gene encodes the alpha-1A-adrenergic receptor. Alternative splicing of this gene generates four transcript variants, which encode four different isoforms with distinct C-termini but having similar ligand binding properties.[2]
Ligands
Agonists
- 6-(5-fluoro-2-pyrimidin-5-yl-phenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole: EC50 = 1nM, Emax = 65%; good selectivity over α1B, α1D and α2A subtypes[3]
- further partial agonistic imidazole compounds[4][5]
- A-61603[6]
- Metaraminol
Antagonists
- Tamsulosin: for treatment of benign prostatic hyperplasia
- Silodosin: for treatment of benign prostatic hyperplasia
- Doxazosin: for treatment of benign prostatic hyperplasia and/or Hypertension
- Risperidone: used to treat schizophrenia and bipolar disorder
- WB-4101
- Ziprasidone
- Nicergoline
- Most tricyclic antidepressants
Role in neural circuits
α1A-adrenergic receptor subtypes increase inhibition at dendrodendritic synapses, suggesting a synaptic mechanism for noradrenergic modulation of olfactory driven behaviors.[7]
See also
References
- ↑ Langer SZ (1998). "Nomenclature and state of the art on alpha1-adrenoceptors". Eur. Urol. 33 (Suppl 2): 2–6. doi:10.1159/000052227. PMID 9556189.
- ↑ 2.0 2.1 "Entrez Gene: ADRA1A adrenergic, alpha-1A-, receptor". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=148.
- ↑ "6,7-Dihydro-5H-pyrrolo[1,2-a] imidazoles as potent and selective alpha(1A) adrenoceptor partial agonists". Bioorg. Med. Chem. Lett. 19 (11): 3113–7. April 2009. doi:10.1016/j.bmcl.2009.03.166. PMID 19414260.
- ↑ "Potent and selective alpha(1A) adrenoceptor partial agonists-Novel imidazole frameworks". Bioorg. Med. Chem. Lett. 19 (11): 3118–21. April 2009. doi:10.1016/j.bmcl.2009.03.162. PMID 19394220.
- ↑ "Novel 2-imidazoles as potent, selective and CNS penetrant alpha1A adrenoceptor partial agonists". Bioorg. Med. Chem. Lett. 18 (24): 6437–40. December 2008. doi:10.1016/j.bmcl.2008.10.066. PMID 18980842.
- ↑ "A-61603, a potent alpha 1-adrenergic receptor agonist, selective for the alpha 1A receptor subtype". J. Pharmacol. Exp. Ther. 274 (1): 97–103. 1995. PMID 7616455.
- ↑ "α(1A)-Adrenergic regulation of inhibition in the olfactory bulb". J. Physiol. 591 (Pt 7): 1631–43. 2013. doi:10.1113/jphysiol.2012.248591. PMID 23266935.
External links
- "α1A-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2175.
- Human ADRA1A genome location and ADRA1A gene details page in the UCSC Genome Browser.
Further reading
- "Alpha-adrenergic approach in the medical management of benign prostatic hyperplasia". Med Res Rev 17 (6): 523–35. 1998. doi:10.1002/(SICI)1098-1128(199711)17:6<523::AID-MED2>3.0.CO;2-3. PMID 9359081.
- "A two-allele PstI RFLP for the alpha-1C adrenergic receptor gene (ADRA1C)". Hum. Mol. Genet. 1 (5): 349. 1993. doi:10.1093/hmg/1.5.349-a. PMID 1363873.
- "Molecular cloning and expression of the cDNA for a novel alpha 1-adrenergic receptor subtype". J. Biol. Chem. 265 (14): 8183–9. 1990. doi:10.1016/S0021-9258(19)39055-6. PMID 1970822.
- "Cloning, functional expression and tissue distribution of human alpha 1c-adrenoceptor splice variants". FEBS Lett. 363 (3): 256–60. 1995. doi:10.1016/0014-5793(95)00330-C. PMID 7737411.
- "Identification of the alpha 1c-adrenoceptor in rabbit arteries and the human saphenous vein using the polymerase chain reaction". Eur. J. Pharmacol. 268 (3): 393–8. 1995. doi:10.1016/0922-4106(94)90064-7. PMID 7805763.
- "Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues". J. Pharmacol. Exp. Ther. 272 (1): 134–42. 1995. PMID 7815325.
- "Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c". Biochem. Biophys. Res. Commun. 201 (3): 1296–304. 1994. doi:10.1006/bbrc.1994.1845. PMID 8024574.
- "The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype". Mol. Pharmacol. 45 (4): 703–8. 1994. PMID 8183249.
- "Cloning, functional expression and tissue distribution of human cDNA for the alpha 1C-adrenergic receptor". Biochem. Biophys. Res. Commun. 195 (2): 902–9. 1993. doi:10.1006/bbrc.1993.2130. PMID 8396931.
- "The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types". Br. J. Pharmacol. 115 (8): 1475–85. 1996. doi:10.1111/j.1476-5381.1995.tb16640.x. PMID 8564208.
- "Alpha 1a-adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy". Br. J. Pharmacol. 118 (6): 1403–8. 1997. doi:10.1111/j.1476-5381.1996.tb15552.x. PMID 8832064.
- "Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms". FEBS Lett. 422 (2): 279–83. 1998. doi:10.1016/S0014-5793(98)00024-6. PMID 9490024.
- "Human cloned alpha1A-adrenoceptor isoforms display alpha1L-adrenoceptor pharmacology in functional studies". Eur. J. Pharmacol. 370 (3): 337–43. 1999. doi:10.1016/S0014-2999(99)00154-5. PMID 10334511.
- "Truncated isoforms inhibit 3Hprazosin binding and cellular trafficking of native human alpha1A-adrenoceptors". Biochem. J. 343 Pt 1 (Pt 1): 231–9. 1999. doi:10.1042/0264-6021:3430231. PMID 10493934.
- "Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age". Circulation 100 (23): 2336–43. 1999. doi:10.1161/01.cir.100.23.2336. PMID 10587338.
- "Differential regulation of the phosphatidylinositol 3-kinase/Akt and p70 S6 kinase pathways by the alpha(1A)-adrenergic receptor in rat-1 fibroblasts". J. Biol. Chem. 275 (7): 4803–9. 2000. doi:10.1074/jbc.275.7.4803. PMID 10671514.
- "alpha(1)-adrenoceptor subtypes differentially couple to growth promotion and inhibition in Chinese hamster ovary cells". Biochem. Biophys. Res. Commun. 272 (3): 906–11. 2000. doi:10.1006/bbrc.2000.2850. PMID 10860850.
- "Agonist-regulated Interaction between alpha2-adrenergic receptors and spinophilin". J. Biol. Chem. 276 (18): 15003–8. 2001. doi:10.1074/jbc.M011679200. PMID 11154706.
- "alpha 1-Adrenergic receptor subtypes differentially control the cell cycle of transfected CHO cells through a cAMP-dependent mechanism involving p27Kip1". J. Biol. Chem. 278 (1): 672–8. 2003. doi:10.1074/jbc.M201375200. PMID 12409310.
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