• 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 disc • 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 • smooth muscle contraction • 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
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[8]
further partial agonistic imidazole compounds[9][10]
^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.
^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.
^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.
^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.
^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
. 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.
一月 14, 2023
肾上腺素受体α1a, α1a, adrenoreceptor, 又稱為adra1a, 是一種α1肾上腺素受体, 英语, alpha, adrenergic, receptor, 過去一度有α1c的分類, 但在研究後認為α1c僅是α1a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, 識別號别名adra1a, adra1c, adra1l1, alpha1aar, adrenoceptor, alpha, 1a外部idomim, 104221, 104773, homologene. 肾上腺素受体a1A a1A adrenoreceptor 又稱為ADRA1A 6 是一種a1肾上腺素受体 英语 alpha 1 adrenergic receptor 7 過去一度有a1C的分類 但在研究後認為a1C僅是a1A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a1A識別號别名ADRA1A ADRA1C ADRA1L1 ALPHA1AAR adrenoceptor alpha 1A外部IDOMIM 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 維思通 ritanserin roxindole 西洛多辛 spiperone spiroxatrine 坦索羅辛 定脈平 terguride WB 4101 哌唯嗪 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 disc 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 smooth muscle contraction 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 signalingSources Amigo QuickGO直系同源物種人類小鼠Entrez14811549EnsemblENSG00000120907ENSMUSG00000045875UniProtP35348P97718mRNA 序列 NM 000680 NM 033302 NM 033303 NM 033304 NM 001322502 NM 001322503 NM 001322504NM 001271759 NM 001271760 NM 001271761 NM 013461蛋白序列NP 000671 NP 001309431 NP 001309432 NP 001309433 NP 150645 NP 150646 NP 150647NP 001258688 NP 001258689 NP 001258690 NP 038489基因位置 UCSC Chr 8 26 75 26 87 MbChr 14 66 87 67 01 MbPubMed 查找 4 5 維基數據檢視 編輯人類檢視 編輯小鼠 目录 1 受體 2 基因 3 配體 3 1 致效劑 3 2 受體拮抗劑 4 在神經迴路的角色 5 參見 6 參考文獻 7 外部連結 8 延伸閱讀受體 编辑肾上腺素受体a1共有3種亞型 包含a1A a1B a1D 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 编辑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 编辑致效劑 编辑 6 5 fluoro 2 pyrimidin 5 yl phenyl 6 7 dihydro 5H pyrrolo 1 2 a imidazole EC50 1nM Emax 65 good selectivity over a1B a1D and a2A subtypes 8 further partial agonistic imidazole compounds 9 10 A 61603 11 受體拮抗劑 编辑 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 英语 Ziprasidone 在神經迴路的角色 编辑肾上腺素受体a1A可加強對於樹樹突觸的抑制 12 參見 编辑肾上腺素受体參考文獻 编辑 對Adrenoceptor alpha 1A起作用的藥物 在維基數據上查看 編輯參考 2 0 2 1 2 2 GRCh38 Ensembl release 89 ENSG00000120907 Ensembl May 2017 3 0 3 1 3 2 GRCm38 Ensembl release 89 ENSMUSG00000045875 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine 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 0 7 1 Entrez Gene ADRA1A adrenergic alpha 1A receptor 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 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 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 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 Zimnik NC Treadway T Smith RS Araneda RC a 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 编辑a1A 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 编辑Matyus P Horvath 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 lt 523 AID MED2 gt 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 Coge 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 取自 https zh wikipedia org w index php title 肾上腺素受体a1A amp oldid 72697472, 维基百科，wiki，书籍，书籍，图书馆，
