肾上腺素受体α1A

肾上腺素受体α_1A（α_1A adrenoreceptor），又稱為ADRA1A^[6]，是一種α1肾上腺素受体（英语：alpha-1 adrenergic receptor）^[7]。過去一度有α_1C的分類，但在研究後認為α_1C僅是α_1A的一種亞型，因此取消該命名。為了避免混淆，之後新發現的亞型便從D開始繼續命名。

肾上腺素受体α1A
識別號
别名	ADRA1A；, ADRA1C, ADRA1L1, ALPHA1AAR, adrenoceptor alpha 1A
外部ID	OMIM：104221 MGI：104773 HomoloGene：68078 GeneCards：ADRA1A
為以下藥物的標靶
肾上腺素、​甲氧明、​去甲肾上腺素、​羟甲唑啉、​脫羥腎上腺素、​地西泮、​阿夫唑嗪、​BMY-7378、​過乳降、​氯氮平、​希普利敏、​可迅、​indoramin、​酮色林、​麥角乙脲、​米塞林、​NAN 190、​苄胺唑啉、​吡貝地爾、​利培酮、​ritanserin、​roxindole、​赛洛多辛、​spiperone、​spiroxatrine、​坦索羅辛、​定脈平、​特麦角脲、​WB-4101、​哌唯嗪、​異蘇氨酸、​肾上腺素、​去甲肾上腺素、​麻黃鹼、​methoxamine hydrochloride、​dabuzalgron、​dipivefrin hydrochloride、​多沙唑嗪甲磺酸盐、​oxymetazoline hydrochloride、​phenoxybenzamine hydrochloride、​phenylephrine hydrochloride、​prazosin hydrochloride、​tamsulosin hydrochloride、​midodrine hydrochloride、​alfuzosin hydrochloride[1]
基因位置（人类） 染色体 8號染色體[2] 基因座 8p21.2 起始 26,748,150 bp[2] 终止 26,867,278 bp[2]
基因位置（小鼠） 染色体 小鼠14号染色体[3] 基因座 14|14 D1 起始 66,872,700 bp[3] 终止 67,008,617 bp[3]
RNA表达模式
查阅更多表达数据
基因本體 分子功能 • signal transducer activity • adrenergic receptor activity • protein heterodimerization activity • G protein-coupled receptor activity • alpha1-adrenergic receptor activity • 血浆蛋白结合 細胞組分 • 横小管 • 核膜 • integral component of membrane • 细胞核 • integral component of plasma membrane • 膜 • Z discdkac • 细胞膜 • 細胞質 • caveola • dopaminergic synapse • glutamatergic synapse • GABA-ergic synapse • integral component of postsynaptic membrane • integral component of presynaptic membrane 生物學過程 • positive regulation of cardiac muscle contraction • negative regulation of cell population proliferation • response to hormone • norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure • positive regulation of MAPK cascade • intracellular signal transduction • positive regulation of ERK1 and ERK2 cascade • 訊息傳遞 • organ growth • cell-cell signaling • positive regulation of smooth muscle contraction • activation of phospholipase C activity • pilomotor reflex • regulation of vasoconstriction • positive regulation of heart rate • positive regulation of synaptic transmission, GABAergic • positive regulation of systemic arterial blood pressure • G protein-coupled receptor signaling pathway • 排尿 • calcium ion transport into cytosol • positive regulation of action potential • positive regulation of the force of heart contraction by epinephrine-norepinephrine • 细胞凋亡 • 平滑肌收缩 • phospholipase C-activating G protein-coupled receptor signaling pathway • adenylate cyclase-activating adrenergic receptor signaling pathway • 老化 • regulation of cardiac muscle contraction • positive regulation of heart rate by epinephrine-norepinephrine • positive regulation of protein kinase C signaling • negative regulation of Rho protein signal transduction • regulation of muscle contraction • adult heart development • negative regulation of heart rate involved in baroreceptor response to increased systemic arterial blood pressure • positive regulation of cytosolic calcium ion concentration • positive regulation of vasoconstriction • negative regulation of autophagy • positive regulation of cardiac muscle hypertrophy • positive regulation of non-membrane spanning protein tyrosine kinase activity • cell growth involved in cardiac muscle cell development • regulation of synaptic vesicle exocytosis • adenylate cyclase-modulating G protein-coupled receptor signaling pathway • neuron-glial cell signaling Sources:Amigo / QuickGO
直系同源
物種	人類	小鼠
Entrez	148	11549
Ensembl	ENSG00000120907	ENSMUSG00000045875
UniProt	P35348	P97718
mRNA​序列	​NM_000680 ​NM_033302 ​NM_033303 ​NM_033304 ​NM_001322502 ​NM_001322503 ​NM_001322504	NM_001271759 ​NM_001271760 ​NM_001271761 ​NM_013461
蛋白序列	NP_000671 ​NP_001309431 ​NP_001309432 ​NP_001309433 ​NP_150645 ​NP_150646 ​NP_150647	NP_001258688 ​NP_001258689 ​NP_001258690 ​NP_038489
基因位置​（UCSC）	Chr 8: 26.75 – 26.87 Mb	Chr 14: 66.87 – 67.01 Mb
PubMed​查找	[4]	[5]
維基數據
檢視/編輯人類 檢視/編輯小鼠

受體

肾上腺素受体α₁共有3種亞型，包含α_1A、α_1B、α_1D，全都屬於Gq/11家族的G蛋白。不同亞型的致活路徑有所差異，本類受體在體內主要內源性配體為腎上腺素，主要產生战斗或逃跑反应。

基因

該蛋白的基因共有四種剪切方式，因此共有四種同型體。不同同型體可由其C端判別，但基本上功能相同^[7]。

配體

致效劑

• 6-(5-fluoro-2-pyrimidin-5-yl-phenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole: EC₅₀ = 1nM, E_max = 65%; good selectivity over α1B, α1D and α2A subtypes^[8]
• further partial agonistic imidazole compounds^[9][10]
• A-61603^[11]

受體拮抗劑

• Tamsulosin：用於治療良性前列腺增生症
• Silodosin（英语：Silodosin）：用於治療良性前列腺增生症
• 維思通
• WB-4101
• Ziprasidone

在神經迴路的角色

肾上腺素受体α1A可加強對於樹樹突觸的抑制^[12]。

參見

• 肾上腺素受体

參考文獻

1. 對Adrenoceptor alpha 1A起作用的藥物；在維基數據上查看/編輯參考.
2. GRCh38: Ensembl release 89: ENSG00000120907 - Ensembl, May 2017
3. GRCm38: Ensembl release 89: ENSMUSG00000045875 - Ensembl, May 2017
4. Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
6. Langer SZ. Nomenclature and state of the art on alpha1-adrenoceptors. Eur. Urol. 1998,. 33 Suppl 2: 2–6. PMID 9556189. doi:10.1159/000052227.
7. Entrez Gene: ADRA1A adrenergic, alpha-1A-, receptor.
8. Roberts LR, Fish PV, Ian Storer R, Whitlock GA. 6,7-Dihydro-5H-pyrrolo[1,2-a] imidazoles as potent and selective alpha(1A) adrenoceptor partial agonists. Bioorg. Med. Chem. Lett. April 2009, 19 (11): 3113–7. PMID 19414260. doi:10.1016/j.bmcl.2009.03.166.
9. Whitlock GA, Brennan PE, Roberts LR, Stobie A. Potent and selective alpha(1A) adrenoceptor partial agonists-Novel imidazole frameworks. Bioorg. Med. Chem. Lett. April 2009, 19 (11): 3118–21. PMID 19394220. doi:10.1016/j.bmcl.2009.03.162.
10. Roberts LR, Bryans J, Conlon K, McMurray G, Stobie A, Whitlock GA. Novel 2-imidazoles as potent, selective and CNS penetrant alpha1A adrenoceptor partial agonists. Bioorg. Med. Chem. Lett. December 2008, 18 (24): 6437–40. PMID 18980842. doi:10.1016/j.bmcl.2008.10.066.
11. Knepper SM, Buckner SA, Brune ME, DeBernardis JF, Meyer MD, Hancock AA. A-61603, a potent alpha 1-adrenergic receptor agonist, selective for the alpha 1A receptor subtype. J. Pharmacol. Exp. Ther. 1995, 274 (1): 97–103. PMID 7616455.
12. Zimnik NC, Treadway T, Smith RS, Araneda RC. α(1A)-Adrenergic regulation of inhibition in the olfactory bulb. J. Physiol. (Lond.). 2013, 591 (Pt 7): 1631–43. PMC 3624843 . PMID 23266935. doi:10.1113/jphysiol.2012.248591.

外部連結

• α_1A-adrenoceptor. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. （原始内容存档于2020-11-22）.

延伸閱讀

• Mátyus P, Horváth K. Alpha-adrenergic approach in the medical management of benign prostatic hyperplasia. Med Res Rev. 1998, 17 (6): 523–35. PMID 9359081. doi:10.1002/(SICI)1098-1128(199711)17:6<523::AID-MED2>3.0.CO;2-3.
• Hoehe MR, Berrettini WH, Schwinn DA, Hsieh WT. A two-allele PstI RFLP for the alpha-1C adrenergic receptor gene (ADRA1C). Hum. Mol. Genet. 1993, 1 (5): 349. PMID 1363873. doi:10.1093/hmg/1.5.349-a.
• Schwinn DA, Lomasney JW, Lorenz W, et al. Molecular cloning and expression of the cDNA for a novel alpha 1-adrenergic receptor subtype. J. Biol. Chem. 1990, 265 (14): 8183–9. PMID 1970822.
• Hirasawa A, Shibata K, Horie K, et al. Cloning, functional expression and tissue distribution of human alpha 1c-adrenoceptor splice variants. FEBS Lett. 1995, 363 (3): 256–60. PMID 7737411. doi:10.1016/0014-5793(95)00330-C.
• Diehl NL, Shreeve SM. Identification of the alpha 1c-adrenoceptor in rabbit arteries and the human saphenous vein using the polymerase chain reaction. Eur. J. Pharmacol. 1995, 268 (3): 393–8. PMID 7805763. doi:10.1016/0922-4106(94)90064-7.
• Schwinn DA, Johnston GI, Page SO, et al. Cloning and pharmacological characterization of human alpha-1 adrenergic receptors: sequence corrections and direct comparison with other species homologues. J. Pharmacol. Exp. Ther. 1995, 272 (1): 134–42. PMID 7815325.
• Weinberg DH, Trivedi P, Tan CP, et al. Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c. Biochem. Biophys. Res. Commun. 1994, 201 (3): 1296–304. PMID 8024574. doi:10.1006/bbrc.1994.1845.
• Forray C, Bard JA, Wetzel JM, et al. 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. 1994, 45 (4): 703–8. PMID 8183249.
• Hirasawa A, Horie K, Tanaka T, et al. Cloning, functional expression and tissue distribution of human cDNA for the alpha 1C-adrenergic receptor. Biochem. Biophys. Res. Commun. 1993, 195 (2): 902–9. PMID 8396931. doi:10.1006/bbrc.1993.2130.
• Tseng-Crank J, Kost T, Goetz A, et al. The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types. Br. J. Pharmacol. 1996, 115 (8): 1475–85. PMC 1908895 . PMID 8564208. doi:10.1111/j.1476-5381.1995.tb16640.x.
• Shibata K, Hirasawa A, Moriyama N, et al. Alpha 1a-adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy. Br. J. Pharmacol. 1997, 118 (6): 1403–8. PMC 1909672 . PMID 8832064. doi:10.1111/j.1476-5381.1996.tb15552.x.
• Chang DJ, Chang TK, Yamanishi SS, et al. Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms. FEBS Lett. 1998, 422 (2): 279–83. PMID 9490024. doi:10.1016/S0014-5793(98)00024-6.
• Daniels DV, Gever JR, Jasper JR, et al. Human cloned alpha1A-adrenoceptor isoforms display alpha1L-adrenoceptor pharmacology in functional studies. Eur. J. Pharmacol. 1999, 370 (3): 337–43. PMID 10334511. doi:10.1016/S0014-2999(99)00154-5.
• Cogé F, Guenin SP, Renouard-Try A, et al. Truncated isoforms inhibit 3Hprazosin binding and cellular trafficking of native human alpha1A-adrenoceptors. Biochem. J. 1999,. 343 Pt 1 (Pt 1): 231–9. PMC 1220546 . PMID 10493934. doi:10.1042/0264-6021:3430231.
• Rudner XL, Berkowitz DE, Booth JV, et al. Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age. Circulation. 1999, 100 (23): 2336–43. PMID 10587338. doi:10.1161/01.cir.100.23.2336.
• Ballou LM, Cross ME, Huang S, et al. 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. 2000, 275 (7): 4803–9. PMID 10671514. doi:10.1074/jbc.275.7.4803.
• Keffel S, Alexandrov A, Goepel M, Michel MC. alpha(1)-adrenoceptor subtypes differentially couple to growth promotion and inhibition in Chinese hamster ovary cells. Biochem. Biophys. Res. Commun. 2000, 272 (3): 906–11. PMID 10860850. doi:10.1006/bbrc.2000.2850.
• Richman JG, Brady AE, Wang Q, et al. Agonist-regulated Interaction between alpha2-adrenergic receptors and spinophilin. J. Biol. Chem. 2001, 276 (18): 15003–8. PMID 11154706. doi:10.1074/jbc.M011679200.
• Shibata K, Katsuma S, Koshimizu T, et al. alpha 1-Adrenergic receptor subtypes differentially control the cell cycle of transfected CHO cells through a cAMP-dependent mechanism involving p27Kip1. J. Biol. Chem. 2003, 278 (1): 672–8. PMID 12409310. doi:10.1074/jbc.M201375200.