Alfa-1A adrenergički receptor

Adrenergički alfa-1A receptor
Identifikatori
Simboli ADRA1A; ADRA1C; ADRA1L1; ALPHA1AAR
Vanjski ID OMIM: 104221 MGI: 104773 HomoloGene: 68078 IUPHAR: α1A-adrenoceptor GeneCards: ADRA1A Gene
Ontologija gena
Molekularna funkcija • aktivnost rodopsinu-sličnog receptora
• receptorska aktivnost
• aktivnost adrenoceptora
• aktivnost alfa1-adrenergičkog receptora
Celularna komponenta • integralno sa ćelijskom membranom
• membrana
Biološki proces • apoptoza
• kontrakcija glatkog mišića
• prenos signala
• signalni put G-protein spregnutog receptora
• kaskada proteinskih kinaza
• interćelijska signalizacija
• negativna regulacija ćelijske proliferacije
Pregled RNK izražavanja
podaci
Ortolozi
Vrsta Čovek Miš
Entrez 148 11549
Ensembl ENSG00000120907 ENSMUSG00000045875
UniProt P35348 Q8BUE5
RefSeq (mRNA) NM_000680 NM_013461
RefSeq (protein) NP_000671 NP_038489
Lokacija (UCSC) Chr 8:
26.66 - 26.78 Mb		 Chr 14:
65.59 - 65.69 Mb
PubMed pretraga [1] [2]

Alfa-1A adrenergički receptor (α1A adrenoreceptor, ADRA1A, alfa-1C adrenergički receptor) je alfa-1 adrenergički receptor. On je kodiran ADRA1A humanim genom.[1][2]

Receptor

Postoje 3 tipa alfa-1 adrenergičkog receptora: alfa-1A, -1B i -1D, svi od kojih prenose signal kroz Gq/11 familiju G-proteina. Različiti podtipovi pokazuju različite oblike aktivacije.

Gen

Alternativno splajsovanje ovog gena proizvodi različite transkriptne varijante, koje kodiraju četiri izoforme sa distinktinim C-terminusima. One imaju slična svojstva u pogledu vezivanja liganda.[1]

Ligandi

Agonisti

  • 6-(5-fluoro-2-pirimidin-5-il-fenil)-6,7-dihidro-5H-pirolo[1,2-a]imidazol EC50 = 1nM, Emax = 65%; dobra selektivnost u odnosu na α1B, α1D i α2A tipove[3]
  • više parcijalnih agonista sa imidazolnom osnovom[4][5]

Antagonisti

Vidi još

Literatura

  1. ^ а б „Entrez Gene: ADRA1A adrenergic, alpha-1A-, receptor”. 
  2. ^ SZ, Langer (1998). „Nomenclature and state of the art on alpha1-adrenoceptors”. Eur. Urol. 33 Suppl 2: 2—6. PMID 9556189. doi:10.1159/000052227. 
  3. ^ Roberts LR, Fish PV, Ian Storer R, Whitlock GA (2009). „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. PMID 19414260. doi:10.1016/j.bmcl.2009.03.166. 
  4. ^ Whitlock GA, Brennan PE, Roberts LR, Stobie A (2009). „Potent and selective alpha(1A) adrenoceptor partial agonists-Novel imidazole frameworks”. Bioorg. Med. Chem. Lett. 19 (11): 3118. PMID 19394220. doi:10.1016/j.bmcl.2009.03.162. 
  5. ^ Roberts LR, Bryans J, Conlon K, McMurray G, Stobie A, Whitlock GA (2008). „Novel 2-imidazoles as potent, selective and CNS penetrant alpha1A adrenoceptor partial agonists”. Bioorg. Med. Chem. Lett. 18 (24): 6437—40. PMID 18980842. doi:10.1016/j.bmcl.2008.10.066. 

Further reading

  • Mátyus P, Horváth K (1998). „Alpha-adrenergic approach in the medical management of benign prostatic hyperplasia.”. Med Res Rev. 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 (1993). „A two-allele PstI RFLP for the alpha-1C adrenergic receptor gene (ADRA1C).”. Hum. Mol. Genet. 1 (5): 349. PMID 1363873. doi:10.1093/hmg/1.5.349-a. 
  • DA, Schwinn; Lomasney JW; Lorenz W (1990). „Molecular cloning and expression of the cDNA for a novel alpha 1-adrenergic receptor subtype.”. J. Biol. Chem. 265 (14): 8183—9. PMID 1970822. 
  • A, Hirasawa; Shibata K; Horie K (1995). „Cloning, functional expression and tissue distribution of human alpha 1c-adrenoceptor splice variants.”. FEBS Lett. 363 (3): 256—60. PMID 7737411. doi:10.1016/0014-5793(95)00330-C. 
  • Diehl NL, Shreeve SM (1995). „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. PMID 7805763. 
  • DA, Schwinn; Johnston GI; Page SO (1995). „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. PMID 7815325. 
  • DH, Weinberg; Trivedi P; Tan CP (1994). „Cloning, expression and characterization of human alpha adrenergic receptors alpha 1a, alpha 1b and alpha 1c.”. Biochem. Biophys. Res. Commun. 201 (3): 1296—304. PMID 8024574. doi:10.1006/bbrc.1994.1845. 
  • C, Forray; Bard JA; Wetzel JM (1994). „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. PMID 8183249. 
  • A, Hirasawa; Horie K; Tanaka T (1993). „Cloning, functional expression and tissue distribution of human cDNA for the alpha 1C-adrenergic receptor.”. Biochem. Biophys. Res. Commun. 195 (2): 902—9. PMID 8396931. doi:10.1006/bbrc.1993.2130. 
  • Tseng-Crank J; Kost T; Goetz A (1996). „The alpha 1C-adrenoceptor in human prostate: cloning, functional expression, and localization to specific prostatic cell types.”. Br. J. Pharmacol. 115 (8): 1475—85. PMC 1908895 Слободан приступ. PMID 8564208. 
  • K, Shibata; Hirasawa A; Moriyama N (1997). „Alpha 1a-adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy.”. Br. J. Pharmacol. 118 (6): 1403—8. PMC 1909672 Слободан приступ. PMID 8832064. 
  • DJ, Chang; Chang TK; Yamanishi SS (1998). „Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms.”. FEBS Lett. 422 (2): 279—83. PMID 9490024. doi:10.1016/S0014-5793(98)00024-6. 
  • DV, Daniels; Gever JR; Jasper JR (1999). „Human cloned alpha1A-adrenoceptor isoforms display alpha1L-adrenoceptor pharmacology in functional studies.”. Eur. J. Pharmacol. 370 (3): 337—43. PMID 10334511. doi:10.1016/S0014-2999(99)00154-5. 
  • F, Cogé; Guenin SP; Renouard-Try A (1999). „Truncated isoforms inhibit [3H]prazosin binding and cellular trafficking of native human alpha1A-adrenoceptors.”. Biochem. J. 343 Pt 1: 231—9. PMC 1220546 Слободан приступ. PMID 10493934. doi:10.1042/0264-6021:3430231. 
  • XL, Rudner; Berkowitz DE; Booth JV (1999). „Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age.”. Circulation. 100 (23): 2336—43. PMID 10587338. 
  • LM, Ballou; Cross ME; Huang S (2000). „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. PMID 10671514. doi:10.1074/jbc.275.7.4803. 
  • Keffel S, Alexandrov A, Goepel M, Michel MC (2000). „alpha(1)-adrenoceptor subtypes differentially couple to growth promotion and inhibition in Chinese hamster ovary cells.”. Biochem. Biophys. Res. Commun. 272 (3): 906—11. PMID 10860850. doi:10.1006/bbrc.2000.2850. 
  • JG, Richman; Brady AE; Wang Q (2001). „Agonist-regulated Interaction between alpha2-adrenergic receptors and spinophilin.”. J. Biol. Chem. 276 (18): 15003—8. PMID 11154706. doi:10.1074/jbc.M011679200. 
  • K, Shibata; Katsuma S; Koshimizu T (2003). „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. PMID 12409310. doi:10.1074/jbc.M201375200. 

Spoljašnje veze

  • „α1A-adrenoceptor”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Архивирано из оригинала 22. 11. 2020. г. 
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Klasa A: Rodopsinu slični
Neurotransmiter
Adrenergički
α1 (A, B, D) • α2 (A, B, C) • β1 • β2 • β3
Purinski
Adenozinski (A1, A2A, A2B, A3) • P2Y (1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14)
Serotoninski
(svi osim 5-HT3) 5-HT1 (A, B, D, E, F) • 5-HT2 (A, B, C) • 5-HT (4, 5A, 6, 7)
Drugi
Acetilholin (M1, M2, M3, M4, M5) • Dopamin (D1, D2, D3, D4, D5) • Histamin (H1, H2, H3, H4) • Melatonin (1A, 1B, 1C) • TAAR (1, 2, 3, 5, 6, 8, 9)
Metaboliti i
signalni molekuli
Eikozanoidni
CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan
Drugi
Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat • Lizofosfatidna kiselina (1, 2, 3, 4, 5, 6) • Lizofosfolipid (1, 2, 3, 4, 5, 6, 7, 8) • Niacin (1, 2) • Oksoglutarat • PAF • Sfingozin-1-fosfat (1, 2, 3, 4, 5) • Sukcinat
Peptid
Neuropeptidni
B/W (1, 2) • FF (1, 2) • S • Y (1, 2, 4, 5) • Neuromedin (B, U (1, 2)) • Neurotenzin (1, 2)
Drugi
Anafilatoksin (C3a, C5a) • Angiotenzin (1, 2) • Apelin • Bombezin (BRS3, GRPR, NMBR) • Bradikinin (B1, B2) • Hemokin • Holecistokinin (A, B) • Endotelin (A, B) • Formil peptid (1, 2, 3) • FSH • Galanin (1, 2, 3) • GHB receptor • Gonadotropin-oslobađajući hormon (1, 2) • Grelin • Kispeptin • Luteinizirajući hormon/horiogonadotropin • MAS (1, 1L, D, E, F, G, X1, X2, X3, X4) • Melanokortin (1, 2, 3, 4, 5) • MCHR (1, 2) • Motilin • Opioidni (δ, κ, μ, Nociceptin & ζ, ali ne σ) • Oreksin (1, 2) • Oksitocin • Prokineticin (1, 2) • Prolaktin-oslobađajući peptid • Relaksin (1, 2, 3, 4) • Somatostatin (1, 2, 3, 4, 5) • Tahikinin (1, 2, 3) • Tirotropin • Tirotropin-oslobađajući hormon • Urotenzin-II • Vazopresin (1A, 1B, 2)
Razno
Orfan
GPR (1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 81, 82, 83, 84, 85, 87, 88, 92, 101, 103, 109A, 109B, 119, 120, 132, 135, 137B, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 173, 174, 176, 177, 182, 183)
Drugi
Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3)
Klasa B: Sekretinu slični
Orfan
GPR (56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 155, 157)
Drugi
Klasa C: Metabotropni
glutamat / feromon
Ukus
TAS1R (1, 2, 3) • TAS2R (1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 19, 20, 30, 31, 38, 39, 40, 41, 42, 43, 45, 46, 50)
Drugi
Kalcijum-detektujući receptor • GABA B (1, 2) • Glutamatni receptor (Metabotropni glutamat (1, 2, 3, 4, 5, 6, 7, 8)) • GPRC6A • GPR (156, 158, 179) • RAIG (1, 2, 3, 4) • VNR (1, 2, 3, 5)
Klasa F:
Frizzled / Zaglađeni
Uvojiti
Frizzled (1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
Zaglađeni