© 1996 American Heart Association, Inc.
Articles |
1-Adrenergic Receptor Subtypes
Molecular Structure, Function, and Signaling
From the Victor Chang Cardiac Research Institute (R.M.G.), St Vincent's Hospital, Sydney, Australia; the Department of Molecular Cardiology (D.M.P., J.H.), Research Institute, Cleveland (Ohio) Clinic Foundation; the Department of Physiology and Biophysics (R.M.G., J.H.), Case Western Reserve University School of Medicine, Cleveland, Ohio; and the Department of Pharmacology (M.T.P.), University of Kentucky, Lexington.
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Introduction |
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The
1ARs
are important mediators of sympathetic nervous system responses,
particularly those involved in cardiovascular
homeostasis, such as arteriolar smooth muscle constriction and cardiac
contraction.1 2 In addition, 1ARs have more
recently been implicated in the pathogenesis of cardiac
hypertrophy, in ischemia-induced cardiac
arrhythmias, and in ischemic
preconditioning.1 3 Like other ARs, 1ARs
are activated by the catecholamines,
norepinephrine and epinephrine. They are intrinsic
membrane glycoproteins and are members of the GPCR
superfamily.
Over the past 10 to 15 years, data initially based on functional,
radioligand, and biochemical studies have accumulated,
indicating that the 1ARs are a heterogeneous
group of distinct but related proteins. This conclusion has been
confirmed with the molecular cloning of three distinct
1-receptor subtypes, although until recently
discrepancies between the properties of the cloned expressed receptors
and those characterized pharmacologically and biochemically have led to
confusion in the classification of 1-receptor subtypes
and their coupled effector responses.
As detailed in the present review, much of this confusion has now
been clarified for the three cloned 1ARs. These and
other recent insights into the molecular structure, function, and
signaling of 1ARs, the control of
1AR-gene expression, and pharmacological evidence for
additional 1AR subtypes will be reviewed here. For
additional information, the reader is also referred to several previous
reviews of 1ARs.4 5 6 7
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1AR Subtypes
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Functional studies of AR responses, particularly from the laboratories of McGrath8 and Ruffolo,9 provided the initial evidence that there may be subtypes of
1ARs. These studies indicated that postjunctional
responses mediated by 1ARs could not be explained
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A. Ricci, E. Bronzetti, A. Conterno, S. Greco, P. Mulatero, M. Schena, D. Schiavone, S. K. Tayebati, F. Veglio, and F. Amenta {alpha}1-Adrenergic Receptor Subtypes in Human Peripheral Blood Lymphocytes Hypertension, February 1, 1999; 33(2): 708 - 712. [Abstract] [Full Text] [PDF]
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Z.-W. Hu, X.-Y. Shi, R. Z. Lin, and B. B. Hoffman Contrasting Signaling Pathways of {alpha}1A- and {alpha}1B-Adrenergic Receptor Subtype Activation of Phosphatidylinositol 3-Kinase and Ras in Transfected NIH3T3 Cells Mol. Endocrinol., January 1, 1999; 13(1): 3 - 14. [Abstract] [Full Text]
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Y. Ruan, H. Kan, J.-H. Parmentier, S. Fatima, L. F. Allen, and K. U. Malik Alpha-1A Adrenergic Receptor Stimulation with Phenylephrine Promotes Arachidonic Acid Release by Activation of Phospholipase D in Rat-1 Fibroblasts: Inhibition by Protein Kinase A J. Pharmacol. Exp. Ther., February 1, 1998; 284(2): 576 - 585. [Abstract] [Full Text]
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F. R. M. Stassen, R. G. H. T. Maas, P. M. H. Schiffers, G. M. J. Janssen, and J. G. R. De Mey A Positive and Reversible Relationship Between Adrenergic Nerves and Alpha-1A Adrenoceptors in Rat Arteries J. Pharmacol. Exp. Ther., January 1, 1998; 284(1): 399 - 405. [Abstract] [Full Text]
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B. Gao, J. Chen, C. Johnson, and G. Kunos Both the Cyclic AMP Response Element and the Activator Protein 2 Binding Site Mediate Basal and Cyclic AMP-Induced Transcription from the Dominant Promoter of the Rat alpha 1B-Adrenergic Receptor Gene in DDT1MF-2 Cells Mol. Pharmacol., December 1, 1997; 52(6): 1019 - 1026. [Abstract] [Full Text]
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M. A. Razik, K. Lee, R. R. Price, M. R. Williams, R. R. Ongjoco, M. K. Dole, X. L. Rudner, M. M. Kwatra, and D. A. Schwinn Transcriptional Regulation of the Human alpha 1a-Adrenergic Receptor Gene. CHARACTERIZATION OF THE 5'-REGULATORY AND PROMOTER REGION J. Biol. Chem., November 7, 1997; 272(45): 28237 - 28246. [Abstract] [Full Text] [PDF]
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M. T. Piascik, S. L. Hrometz, S. E. Edelmann, R. D. Guarino, R. W. Hadley, and R. D. Brown Immunocytochemical Localization of the Alpha-1B Adrenergic Receptor and the Contribution of This and the Other Subtypes to Vascular Smooth Muscle Contraction: Analysis with Selective Ligands and Antisense Oligonucleotides J. Pharmacol. Exp. Ther., November 1, 1997; 283(2): 854 - 868. [Abstract] [Full Text]
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J. Vazquez-Prado, L. d. C. Medina, and J. A. Garcia-Sainz Activation of Endothelin ETA Receptors Induces Phosphorylation of alpha 1b-Adrenoreceptors in Rat-1 Fibroblasts J. Biol. Chem., October 24, 1997; 272(43): 27330 - 27337. [Abstract] [Full Text] [PDF]
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J. Chen, M. S. Spector, G. Kunos, and B. Gao Sp1-mediated Transcriptional Activation from the Dominant Promoter of the Rat alpha 1B Adrenergic Receptor Gene in DDT1MF-2 Cells J. Biol. Chem., September 12, 1997; 272(37): 23144 - 23150. [Abstract] [Full Text] [PDF]
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A. D. Eckhart, N. Yang, X. Xin, and J. E. Faber Characterization of the alpha 1B-adrenergic receptor gene promoter region and hypoxia regulatory elements in vascular smooth muscle PNAS, August 19, 1997; 94(17): 9487 - 9492. [Abstract] [Full Text] [PDF]
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L. C. Hool, L. M. Oleksa, and R. D. Harvey Role of G Proteins in alpha 1-Adrenergic Inhibition of the beta -Adrenergically Activated Chloride Current in Cardiac Myocytes Mol. Pharmacol., May 1, 1997; 51(5): 853 - 860. [Abstract] [Full Text]
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M. L. Clements, A. J. Banes, and J. E. Faber Effect of Mechanical Loading on Vascular {alpha}1D- and {alpha}1B-Adrenergic Receptor Expression Hypertension, May 1, 1997; 29(5): 1156 - 1164. [Abstract] [Full Text]
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M. L. Clements and J. E. Faber Mechanical Load Opposes Angiotensin-Mediated Decrease in Vascular {alpha}1-Adrenoceptors Hypertension, May 1, 1997; 29(5): 1165 - 1172. [Abstract] [Full Text]
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F. R.M. Stassen, M. J.J.M.F. Willemsen, G. M.J. Janssen, and J. G.R. DeMey {alpha}1-Adrenoceptor subtypes in rat aorta and mesenteric small arteries are preserved during left ventricular dysfunction post-myocardial infarction Cardiovasc Res, March 1, 1997; 33(3): 706 - 713. [Abstract] [PDF]
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S. Chen, F. Lin, S. Iismaa, K. N. Lee, P. J. Birckbichler, and R. M. Graham alpha 1-Adrenergic Receptor Signaling via Gh Is Subtype Specific and Independent of Its Transglutaminase Activity J. Biol. Chem., December 13, 1996; 271(50): 32385 - 32391. [Abstract] [Full Text] [PDF]
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K. Ziani, R. Gisbert, M. A. Noguera, M. D. Ivorra, and P. D'Ocon Modulatory role of a constitutively active population of alpha 1D-adrenoceptors in conductance arteries Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H475 - H481. [Abstract] [Full Text] [PDF]
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F. Lin, W. A. Owens, S. Chen, M. E. Stevens, S. Kesteven, J. F. Arthur, E. A. Woodcock, M. P. Feneley, and R. M. Graham Targeted {alpha}1A-Adrenergic Receptor Overexpression Induces Enhanced Cardiac Contractility but not Hypertrophy Circ. Res., August 17, 2001; 89(4): 343 - 350. [Abstract] [Full Text] [PDF]
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