Identification of adrenergic receptor polymorphisms

Small, Kersten M.; Rathz, Deborah A.; Liggett, Stephen B.

doi:10.1016/s0076-6879(02)43152-7

Cited by 38 publications

(23 citation statements)

References 23 publications

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“…The Gly49 allele frequencies were found to differ significantly between controls and patients (see Table 2). The observed allele frequency for controls was found to be in good accordance with a recently reported allele frequency for Caucasians (Small et al 2002a). In summary, we have shown a significant association between Gly49 genotype and heart rate, as well as a significantly different allele frequency between IOI subjects and controls.…”

Section: Discussionsupporting

confidence: 91%

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Functional adrenergic receptor polymorphisms and idiopathic orthostatic intolerance

Winker

Barth

Valic

et al. 2005

Int Arch Occup Environ Health

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Section: Discussionsupporting

confidence: 91%

“…Genomic DNA was isolated from samples of peripheral blood, and the adrenergic receptor polymorphisms were determined exactly as previously described (Small et al 2002a). …”

Section: Genotypingmentioning

confidence: 99%

Functional adrenergic receptor polymorphisms and idiopathic orthostatic intolerance

Winker

Barth

Valic

et al. 2005

Int Arch Occup Environ Health

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“…Another potentially limiting factor for use of b 2 -agonists is the b 2 -adrenergic receptor polymorphism, which might influence the response to the agonists and b 2 AR regulation (121,122). While the effect of b 2 -adrenergic receptor polymorphism in asthma has been studied and has been shown to affect clinical response, it has not been evaluated in the alveolar epithelium of humans (123)(124).…”

Section: Limitationsmentioning

confidence: 99%

Alveolar Epithelial β₂-Adrenergic Receptors

Mutlu

Factor²

2008

Am J Respir Cell Mol Biol

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b 2 -adrenergic receptors are present throughout the lung, including the alveolar airspace, where they play an important role for regulation of the active Na 1 transport needed for clearance of excess fluid out of alveolar airspace. b 2 -adrenergic receptor signaling is required for up-regulation of alveolar epithelial active ion transport in the setting of excess alveolar edema. The positive, protective effects of b 2 -adrenergic receptor signaling on alveolar active Na 1 transport in normal and injured lungs provide substantial support for the use of b-adrenergic agonists to accelerate alveolar fluid clearance in patients with cardiogenic and noncardiogenic pulmonary edema. In this review, we summarize the role of b 2 -adrenergic receptors in the alveolar epithelium with emphasis on their role in the regulation of alveolar active Na 1 transport in normal and injured lungs.Keywords: pulmonary edema; acute respiratory distress syndrome; acute lung injury; alveoli; albuterol b 2 -adrenergic receptors (b 2 AR) are present throughout the lung. In the alveolar airspace they are important for regulation of the active Na 1 transport needed for clearance of excess fluid out of alveolar airspace (1). Both experimental and limited clinical data suggest that b-adrenergic agonists working via the b 2 AR accelerate clearance of excess fluid from the alveolar airspace, creating the possibility of their use for treatment of pulmonary edema and acute lung injury (ALI).In this review, we summarize the role of b 2 -adrenergic receptors in the alveolar epithelium with emphasis on their role in regulation of alveolar active Na 1 transport in normal and injured lungs. We also overview data regarding b 2 -agonist therapy for pulmonary edema and lung injury. In the lung, b2-adrenergic receptor (b 2 AR) expression increases with each airway generation, with the greatest total amounts in the distal airways and alveoli (3). Greater than 90% of all b-adrenergic receptors in human lung are located in the alveoli (4). Although both b 1 and b 2 subtypes coexist and are distributed uniformly in the alveolar walls, the b 2 -subtype predominates (70%) (4). Isolated rat alveolar type II cells possess b 2 AR and data from autoradiographic and immunohistochemical studies support their presence in the alveolar type 1 cells (4, 5). -Adrenergic Receptor Structure and FunctionThe b 2 -adrenergic receptor is a 1,200-base pair, single-copy, intronless gene located on the long arm of human chromosome 5 that encodes a 413-amino acid protein with a molecular mass of approximately 46.5 kD (1). The b 2 -receptor is a prototypical G protein-coupled receptor (GPCR) with seven-transmembrane domains, an extracellular amino terminus, an intracellular carboxyl terminus, three interconnecting extracellular loops, and three intracellular loops.b 2 -adrenergic receptors exist in the plasma membrane in an equilibrium between at least two structural conformations; inactive and active forms that are defined based on their ability to associate with the stimulatory guano...

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“…In one case, the primer utilized for PCRs can be altered such that the combination of a primary PCR induced mutation and the polymorphism results in differential endonuclease digestion. The specific methods have been recently reviewed in detail [10].…”

Section: Identification Of ß 1 Ar and ß 2 Ar Polymorphismsmentioning

confidence: 99%

Pharmacogenetics of Beta-1- and Beta-2-Adrenergic Receptors

Liggett¹

2000

Pharmacology

Self Cite

131

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β₁- and β₂-adrenergic receptors are G protein-coupled receptors expressed throughout the body and serve as receptors for the catecholamines epinephrine and norepinephrine. They are targets for therapeutive agonists and/or antagonists in treatment of heart failure and asthma. Nonsynonymous coding and promoter polymorphisms of both receptors have been identified in the general population. These have been mimicked in transfected cell systems and transgenic mice, and show altered expression, ligand binding, coupling, or regulation phenotypes. Clinical studies to date have revealed that some of these polymorphisms have a significant disease modifying effect or alter the response to treatment. These are some of the first G protein coupled receptor polymorphisms to undergo extensive in vitro study and clinical validation; there are likely to be polymorphisms of other receptors of the superfamily that will have clinical relevance as well.

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Identification of adrenergic receptor polymorphisms

Cited by 38 publications

References 23 publications

Functional adrenergic receptor polymorphisms and idiopathic orthostatic intolerance

Functional adrenergic receptor polymorphisms and idiopathic orthostatic intolerance

Alveolar Epithelial β₂-Adrenergic Receptors

Pharmacogenetics of Beta-1- and Beta-2-Adrenergic Receptors

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Identification of adrenergic receptor polymorphisms

Cited by 38 publications

References 23 publications

Functional adrenergic receptor polymorphisms and idiopathic orthostatic intolerance

Functional adrenergic receptor polymorphisms and idiopathic orthostatic intolerance

Alveolar Epithelial β2-Adrenergic Receptors

Pharmacogenetics of Beta-1- and Beta-2-Adrenergic Receptors

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Product

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Alveolar Epithelial β₂-Adrenergic Receptors