肾上腺素受体α1A

肾上腺素受体α_1A（α_1A adrenoreceptor），又称为ADRA1A^[6]，是一种α1肾上腺素受体（英语：alpha-1 adrenergic receptor）^[7]。过去一度有α_1C的分类，但在研究后认为α_1C仅是α_1A的一种亚型，因此取消该命名。为了避免混淆，之后新发现的亚型便从D开始继续命名。

肾上腺素受体α1A
识别号
别名	ADRA1A；, ADRA1C, ADRA1L1, ALPHA1AAR, adrenoceptor alpha 1A
外部ID	OMIM：104221 MGI：104773 HomoloGene：68078 GeneCards：ADRA1A
为以下药物的标靶
肾上腺素、​甲氧明、​去甲肾上腺素、​羟甲唑啉、​脱羟肾上腺素、​地西泮、​阿夫唑嗪、​BMY-7378、​过乳降、​氯氮平、​希普利敏、​可迅、​indoramin、​酮色林、​麦角乙脲、​米塞林、​NAN 190、​苄胺唑啉、​吡贝地尔、​利培酮、​ritanserin、​roxindole、​赛洛多辛、​spiperone、​spiroxatrine、​坦索罗辛、​定脉平、​特麦角脲、​WB-4101、​哌唯嗪、​异苏氨酸、​肾上腺素、​去甲肾上腺素、​麻黄碱、​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号染色体[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
基因本体 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 细胞组分 • 横小管 • 核膜 • integral component of membrane • 细胞核 • integral component of plasma membrane • 膜 • Z discdkac • 细胞膜 • 细胞质 • caveola • dopaminergic synapse • glutamatergic synapse • GABA-ergic synapse • integral component of postsynaptic membrane • integral component of presynaptic membrane 生物学过程 • 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 • 信号转导 • 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
物种	人类	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]
维基数据
查看/编辑人类 查看/编辑小鼠

受体

肾上腺素受体α₁共有3种亚型，包含α_1A、α_1B、α_1D，全都属于Gq/11家族的G蛋白。不同亚型的致活路径有所差异，本类受体在体内主要内源性配体为肾上腺素，主要产生战斗或逃跑反应。

基因

该蛋白的基因共有四种剪切方式，因此共有四种同型体。不同同型体可由其C端判别，但基本上功能相同^[7]。

配体

致效剂

• 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]

受体拮抗剂

• Tamsulosin：用于治疗良性前列腺增生症
• Silodosin（英语：Silodosin）：用于治疗良性前列腺增生症
• 维思通
• WB-4101
• Ziprasidone

在神经回路的角色

肾上腺素受体α1A可加强对于树树突触的抑制^[12]。

参见

• 肾上腺素受体

参考文献

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.

外部链接

• 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）.

延伸阅读

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• 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.
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