Alpha-1A adrenergic receptor

Adrenoceptor alpha 1A

Identifiers

ADRA1A ; ADRA1C; ADRA1L1; ALPHA1AAR

External IDs

OMIM: 104221 MGI: 104773 HomoloGene: 68078 IUPHAR: 22 ChEMBL: 229 GeneCards: ADRA1A Gene

Gene ontology
Molecular function	• alpha1-adrenergic receptor activity • protein heterodimerization activity
Cellular component	• nucleus • plasma membrane • integral component of plasma membrane • Z disc • T-tubule • nuclear membrane
Biological process	• negative regulation of heart rate involved in baroreceptor response to increased systemic arterial blood pressure • norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure • positive regulation of heart rate by epinephrine-norepinephrine • positive regulation of the force of heart contraction by epinephrine-norepinephrine • positive regulation of systemic arterial blood pressure • apoptotic process • smooth muscle contraction • signal transduction • G-protein coupled receptor signaling pathway • phospholipase C-activating G-protein coupled receptor signaling pathway • activation of phospholipase C activity • positive regulation of cytosolic calcium ion concentration • cell-cell signaling • adult heart development • aging • negative regulation of cell proliferation • response to hormone • cell growth • negative regulation of synaptic transmission, GABAergic • negative regulation of Rho protein signal transduction • organ growth • intracellular signal transduction • response to drug • positive regulation of MAPK cascade • positive regulation of action potential • positive regulation of vasoconstriction • positive regulation of smooth muscle contraction • micturition • calcium ion transport into cytosol • positive regulation of cardiac muscle contraction • positive regulation of ERK1 and ERK2 cascade • adrenergic receptor signaling pathway • positive regulation of protein kinase C signaling • pilomotor reflex
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 8:
26.61 – 26.72 Mb

Chr 14:
66.64 – 66.73 Mb

PubMed search

The alpha-1A adrenergic receptor (α_1A adrenoreceptor), also known as ADRA1A, formerly known as the alpha-1C adrenergic receptor,^[1] is an alpha-1 adrenergic receptor, and also denotes the human gene encoding it.^[2]

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, E_max = 65%; good selectivity over α1B, α1D and α2A subtypes^[3]
further partial agonistic imidazole compounds^[4]^[5]
A-61603^[6]

Antagonists

Tamsulosin: for treatment of benign prostatic hyperplasia
Silodosin: for treatment of benign prostatic hyperplasia
Risperidone
WB-4101

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".
↑ Roberts LR, Fish PV, Ian Storer R, Whitlock GA (April 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): 3113–7. doi:10.1016/j.bmcl.2009.03.166. PMID 19414260.
↑ Whitlock GA, Brennan PE, Roberts LR, Stobie A (April 2009). "Potent and selective alpha(1A) adrenoceptor partial agonists-Novel imidazole frameworks". Bioorg. Med. Chem. Lett. 19 (11): 3118–21. doi:10.1016/j.bmcl.2009.03.162. PMID 19394220.
↑ Roberts LR, Bryans J, Conlon K, McMurray G, Stobie A, Whitlock GA (December 2008). "Novel 2-imidazoles as potent, selective and CNS penetrant alpha1A adrenoceptor partial agonists". Bioorg. Med. Chem. Lett. 18 (24): 6437–40. doi:10.1016/j.bmcl.2008.10.066. PMID 18980842.
↑ Knepper SM, Buckner SA, Brune ME, DeBernardis JF, Meyer MD, Hancock AA (1995). "A-61603, a potent alpha 1-adrenergic receptor agonist, selective for the alpha 1A receptor subtype". J. Pharmacol. Exp. Ther. 274 (1): 97–103. PMID 7616455.

External links

"α_1A-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

Mátyus P, Horváth K (1998). "Alpha-adrenergic approach in the medical management of benign prostatic hyperplasia". Med Res Rev 17 (6): 523–35. doi:10.1002/(SICI)1098-1128(199711)17:6<523::AID-MED2>3.0.CO;2-3. PMID 9359081.
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. doi:10.1093/hmg/1.5.349-a. PMID 1363873.
Schwinn DA, Lomasney JW, Lorenz W et al. (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.
Hirasawa A, Shibata K, Horie K et al. (1995). "Cloning, functional expression and tissue distribution of human alpha 1c-adrenoceptor splice variants". FEBS Lett. 363 (3): 256–60. doi:10.1016/0014-5793(95)00330-C. PMID 7737411.
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. doi:10.1016/0922-4106(94)90064-7. PMID 7805763.
Schwinn DA, Johnston GI, Page SO et al. (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.
Weinberg DH, Trivedi P, Tan CP et al. (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. doi:10.1006/bbrc.1994.1845. PMID 8024574.
Forray C, Bard JA, Wetzel JM et al. (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.
Hirasawa A, Horie K, Tanaka T et al. (1993). "Cloning, functional expression and tissue distribution of human cDNA for the alpha 1C-adrenergic receptor". Biochem. Biophys. Res. Commun. 195 (2): 902–9. doi:10.1006/bbrc.1993.2130. PMID 8396931.
Tseng-Crank J, Kost T, Goetz A et al. (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. doi:10.1111/j.1476-5381.1995.tb16640.x. PMC 1908895. PMID 8564208.
Shibata K, Hirasawa A, Moriyama N et al. (1997). "Alpha 1a-adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy". Br. J. Pharmacol. 118 (6): 1403–8. doi:10.1111/j.1476-5381.1996.tb15552.x. PMC 1909672. PMID 8832064.
Chang DJ, Chang TK, Yamanishi SS et al. (1998). "Molecular cloning, genomic characterization and expression of novel human alpha1A-adrenoceptor isoforms". FEBS Lett. 422 (2): 279–83. doi:10.1016/S0014-5793(98)00024-6. PMID 9490024.
Daniels DV, Gever JR, Jasper JR et al. (1999). "Human cloned alpha1A-adrenoceptor isoforms display alpha1L-adrenoceptor pharmacology in functional studies". Eur. J. Pharmacol. 370 (3): 337–43. doi:10.1016/S0014-2999(99)00154-5. PMID 10334511.
Cogé F, Guenin SP, Renouard-Try A et al. (1999). "Truncated isoforms inhibit 3Hprazosin binding and cellular trafficking of native human alpha1A-adrenoceptors". Biochem. J. 343 Pt 1 (Pt 1): 231–9. doi:10.1042/0264-6021:3430231. PMC 1220546. PMID 10493934.
Rudner XL, Berkowitz DE, Booth JV et al. (1999). "Subtype specific regulation of human vascular alpha(1)-adrenergic receptors by vessel bed and age". Circulation 100 (23): 2336–43. doi:10.1161/01.cir.100.23.2336. PMID 10587338.
Ballou LM, Cross ME, Huang S et al. (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. doi:10.1074/jbc.275.7.4803. PMID 10671514.
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. doi:10.1006/bbrc.2000.2850. PMID 10860850.
Richman JG, Brady AE, Wang Q et al. (2001). "Agonist-regulated Interaction between alpha2-adrenergic receptors and spinophilin". J. Biol. Chem. 276 (18): 15003–8. doi:10.1074/jbc.M011679200. PMID 11154706.
Shibata K, Katsuma S, Koshimizu T et al. (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. doi:10.1074/jbc.M201375200. PMID 12409310.

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	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)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Adhesion	ADGRG (1 2 3 4 5 6 7)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

Index of signal transduction

Description	Intercellular neuropeptides growth factors cytokines hormones Cell surface receptors ligand-gated enzyme-linked G protein-coupled immunoglobulin superfamily integrins neuropeptide growth factor cytokine Intracellular adaptor proteins GTP-binding MAP kinase Calcium signaling Lipid signaling Pathways hedgehog Wnt TGF beta MAPK ERK notch JAK-STAT apoptosis hippo TLR