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ADRA1A Membrane Protein Introduction

Introduction of ADRA1A

Alpha-1-adrenergic receptor (ADRA1A), which is encoded by the ADRA1A gene, is a member of the G protein-coupled receptor superfamily. The translation of ADRA1A is regulated by alpha-1 adrenergic receptors and Monoamine GPCRs. It is associated with a number of diseases including Horner's Syndrome and Ureter cancer. Gene Ontology annotations related to ADRA1A include alpha1-adrenergic receptor activity and G-protein coupled receptor activity. Alpha-1-adrenergic receptors activate mitogenic responses and regulate growth and proliferation of many cells. 3 alpha-1-AR subtypes are alpha1A, alpha1B, and alpha1D receptors. All subtypes signal through the Gq/11 family of G-proteins but show different patterns of activation. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.

Basic Information of ADRA1A
Protein Name Alpha-1A adrenergic receptor
Gene Name ADRA1A
Aliases Alpha-1A adrenoreceptor, Alpha-1A adrenoceptor, Alpha-1C adrenergic receptor, Alpha-adrenergic receptor 1c, ADRA1C
Organism Homo sapiens (Human)
UniProt ID P35348
Transmembrane Times 7
Length (aa) 466
Sequence MVFLSGNASDSSNCTQPPAPVNISKAILLGVILGGLILFGVLGNILVILSVACHRHLHSV
THYYIVNLAVADLLLTSTVLPFSAIFEVLGYWAFGRVFCNIWAAVDVLCCTASIMGLCII
SIDRYIGVSYPLRYPTIVTQRRGLMALLCVWALSLVISIGPLFGWRQPAPEDETICQINE
EPGYVLFSALGSFYLPLAIILVMYCRVYVVAKRESRGLKSGLKTDKSDSEQVTLRIHRKN
APAGGSGMASAKTKTHFSVRLLKFSREKKAAKTLGIVVGCFVLCWLPFFLVMPIGSFFPD
FKPSETVFKIVFWLGYLNSCINPIIYPCSSQEFKKAFQNVLRIQCLCRKQSSKHALGYTL
HPPSQAVEGQHKDMVRIPVGSRETFYRISKTDGVCEWKFFSSMPRGSARITVSKDQSSCT
TARVRSKSFLQVCCCVGPSTPSLDKNHQVPTIKVHTISLSENGEEV

Function of ADRA1A Membrane Protein

Signaling by α1-adrenergic receptors (α1-ARs), in particular, the α1A-subtype, mediate cardioprotective effects in multiple heart failure models. ADRA1A is important in the pathogenesis of hypertension and it can be used as a potential marker of aortic stiffness. α1A-subtype is a therapeutic target to treat right ventricle (RV) failure. It has been shown that chronic adrenergic stimulation produces pain and bladder changes through an ADRA1A mediated mechanism. Thus, ADRA1A stimulation may be an additional trigger for bladder dysfunction presented by the patients. Urethral smooth muscle (USM) contributes to urinary continence by contracting during the urine storage phase, which is mainly mediated by activation of post-junctional α1-adrenoceptors. α1A -adrenoceptor-mediated mechanisms are much less important in females. The differential expression of α1-adrenoceptors in the proximal urethra may contribute to the higher incidence of urinary incontinence in women and obstructed voiding in men.

Model for a1-AR signaling at the nuclear membrane.Fig.1 Model for a1-AR signaling at the nuclear membrane. (O'Connell, 2013)

Application of ADRA1A Membrane Protein in Literature

1. Cowley PM., et al. α1A-Subtype adrenergic agonist therapy for the failing right ventricle. Am J Physiol Heart Circ Physiol. 2017, 313(6): H1109-H1118. PubMed ID: 28822963

This article reports that chronic treatment with the ADRA1A agonist A61603 improves function and survival in the model of left ventricular failure. Such treatment improved right ventricle (RV) contraction and reduced multiple indexes of RV injury, suggesting that ADRA1A is a therapeutic target to treat RV failure.

2. Matos R., et al. The water avoidance stress induces bladder pain due to a prolonged alpha1A adrenoceptor stimulation. Naunyn Schmiedebergs Arch Pharmacol. 2017, 390(8): 839-844. PubMed ID: 28569366

Authors in this group investigate the possible role of ADRA1A in bladder pain and morphological changes. ADRA1A stimulation is essential in the appearance of bladder pain in rats and may be an additional trigger for bladder dysfunction presented by the patients.

3. Alexandre EC., et al. How important is the α1-adrenoceptor in primate and rodent proximal urethra? Sex differences in the contribution of α1-adrenoceptor to urethral contractility. Am J Physiol Renal Physiol. 2017, 312(6): F1026-F1034. PubMed ID: 28298357

This article reports the possible role of α1-adrenoceptor in primate and rodent proximal urethra. It is found that there are sex differences in the contribution of α1-adrenoceptor to urethral contractility, which may contribute to the higher incidence of urinary incontinence in women and obstructed voiding in men.

4. Shi T., et al. α1A-Adrenergic receptor prevents cardiac ischemic damage through PKCδ/GLUT1/4-mediated glucose uptake. J Recept Signal Transduct Res. 2016, 36(3): 261-70. PubMed ID: 26832303

Authors in this group investigate both mouse neonatal and adult myocytes and HL-1 cells in a series of tests assessing ischemic damage under hypoxic or low glucose conditions. The results suggest that ADRA1A prevents cardiac ischemic damage through PKCδ/GLUT1/4-mediated glucose uptake.

5. Goren A., et al. α1 -AR agonist induced piloerection protects against the development of traction alopecia. Dermatol Ther. 2016, 29(3): 160-3. PubMed ID: 26678522

This article demonstrated contraction of the arrector pili muscle via an α1 -AR agonist would increase the threshold of force required to pluck hair during cosmetic procedures. α1-AR agonist (phenylephrine) induced piloerection can be used for treatment of traction alopecia and hair shedding during cosmetic procedures.

ADRA1A Preparation Options

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Reference

  1. O'Connell TD, et al. (2013). Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol Rev. 66(1), 308-33.

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