Genetic polymorphisms of adrenergic receptors

Garland, Emily M.; Biaggioni, Italo

doi:10.1007/bf02322049

Cited by 14 publications

(9 citation statements)

References 103 publications

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“…32 Moreover, different patients have variable adhesive responses to epinephrine ( Figure 3A). This variability may be related to the welldescribed polymorphisms of adrenergic receptors, 33,34 and this possibility is being actively investigated. Similar variability was also reported when the effect of epinephrine on B-CAM/LUmediated adhesion to laminin was studied.…”

Section: Characterization Of the Ss Rbc Adhesive Response To Epinephrinementioning

confidence: 99%

Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-αvβ3 interactions

Zennadi

Hines

Castro

et al. 2004

Blood

134

184

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The possible role of physiologic stress hormones in enhancing adhesion of sickle erythrocytes (SS RBCs) to endothelial cells (ECs) in sickle cell disease (SCD) has not been previously explored. We have now found that up-regulation of intracellular cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) by epinephrine significantly increased sickle but not normal erythrocyte adhesion to both primary and immortalized ECs. Inhibition of serine/threonine phosphatases also enhanced sickle erythrocyte adhesion at least partially through a PKA-dependent mechanism. Adhesion was mediated through LW (intercellular adhesion molecule-4 [ICAM-4], CD242) blood group glycoprotein, and immunoprecipitation studies showed that LW on sickle but not on normal erythrocytes undergoes increased PKA-dependent serine phosphorylation as a result of activation. The major counter receptor for LW was identified as the ␣v␤3 integrin on ECs. These data suggest that adrenergic hormones such as epinephrine may initiate or exacerbate vaso-occlusion and thus contribute to the association of vasoocclusive events with physiologic stress. IntroductionIn sickle cell disease (SCD), abnormal adherence of sickle erythrocytes (SS RBCs) to endothelial cells (ECs) has been postulated to be important in the initiation and/or progression of vaso-occlusive crises. [1][2][3] Although many vaso-occlusive episodes are associated with intercurrent illnesses, and thus with release of endotheliumactivating cytokines such as tumor necrosis factor ␣ (TNF-␣), other vaso-occlusive episodes are associated with other types of stressors. We are interested in exploring whether physiologic stress may precipitate vaso-occlusion via activation of red cell adhesion.Human erythrocytes are equipped with a diversity of receptors and effectors that are known to mediate well-characterized signal transduction pathways in nonerythroid cells. 4 Although activation of adhesion receptors via signal transduction is well accepted in nonerythroid cells, until recently, little attention had been paid to the possibility that abnormal SS RBC adhesion might be mediated via signaling mechanisms inducing activation of RBC adhesion receptors. 5,6 Nevertheless, such events could promote, or even initiate, vaso-occlusion.A variety of stimuli, including epinephrine, have been shown to activate the basal cell adhesion molecule-Lutheran (B-CAM/LU) laminin receptor on SS RBCs through a cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway. 7 Epinephrine is a major stress mediator that elevates cAMP in SS RBCs through stimulation of adrenergic receptors. 7 Cyclic AMP mediates at least some of its effects through activation of PKA. Based on these observations, we postulated that activation of SS RBC adhesion via known signaling pathways might lead to upregulation of SS RBC adhesion to endothelium, even in the absence of plasma bridging proteins. Study of up-regulation of cAMPdependent PKA signaling pathway by epinephrine in SS RBCs has now led to the identificatio...

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Section: Characterization Of the Ss Rbc Adhesive Response To Epinephrinementioning

confidence: 99%

Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-αvβ3 interactions

Zennadi

Hines

Castro

et al. 2004

Blood

134

184

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“…14 The receptor consists of an extracellular amino terminal, seven transmembrane domains and an intracellular carboxyl terminal. 15 The stimulation of catecholamine functions through Ga s receptors to cause a conformational change in the receptor and thus stimulates adenylate cyclase to increase intracellular cAMP. The second messenger system leads to the stimulation of protein kinase A, which phosphorylates endoplasmic reticulum proteins to promote the opening of ligand-gated Ca 2+ channels to facilitate muscular contraction through myosin phosphorylase.…”

Section: Introductionmentioning

confidence: 99%

Adrenergic-β2 receptor polymorphism and athletic performance

Sarpeshkar

Bentley

2010

J Hum Genet

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The focus of this review is to evaluate the influence of b 2 -adrenergic receptor (ADRB2) polymorphism on human physiological function and in turn on athletic performance. A narrative review is conducted on available literature using MedLine, Pubmed and the Cochrane Library to document the location and function of ADRB2 receptors, and specifically to address the influence of genetic polymorphisms on cardiovascular, respiratory, metabolic and musculoskeletal systems and athletic performance. Search terms included ADRB2, endurance and polymorphism. Previous literature exploring the genetic composition of athletes has proposed that alterations in the genetic structure result in an enhancement in their capacity to achieve successful aerobic phenotypes such as a higher VO 2max and increased fat oxidation. Polymorphism of the Gly16Glu27 haplotype is believed to promote positive aerobic phenotypes and regulate optimal lipolysis. Greater knowledge of the ADRB2 polymorphism can aid in understanding the specific phenotypes that are altered, which may influence performance. Until the interaction between fatigue and athletic performance is better understood, the development of appropriate training principles to enhance genetically polymorphic aerobic phenotypes remains complicated. Following the review, there is still no distinctive evidence for the predictive ability of the polymorphism of ADRB2 genotype for the purpose of identifying potential elite athletes.

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“…We identified 7 SNPs of interest occurring in the following 6 genes implicated in vasoregulation: angiotensin II receptor, type 1 (AGTR1); endothelin 1 (EDN1); nitric oxide synthase (endothelial cell) (NOS3); adrenergic, beta-2-, receptor, surface (ADRB2); bradykinin receptor B1 (BDKRB1); and transforming growth factor, beta-1 (TGFB1). [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Priority was given to SNPs demonstrated to be common, functional, and/or repeatedly associated with renal function in the literature in different populations sampled.…”

Section: Measurementsmentioning

confidence: 99%

Endothelial Nitric Oxide Synthase Gene Variation Associated With Chronic Kidney Disease After Liver Transplant

Bambha

Kim

Rosen

et al. 2010

Mayo Clinic Proceedings

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OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after liver transplant (LT). PATIENTS AND METHODS:This study consists of a cohort of adult (≥18 years) primary-LT recipients who had normal renal function before LT and who survived 1 year or more after LT at a high-volume US LT program between January 1, 1990, and December 31, 2000. Patients with adequate renal function (estimated glomerular filtration rate, ≥40 mL/min per 1.73 m 2 during follow-up; n=308) and patients with incident CKD (estimated glomerular filtration rate, <40 mL/min per 1.73 m 2 after LT; n=92) were identified. To investigate the association of 6 candidate genes with post-LT CKD, we selected SNPs that have been associated with renal function in the literature. Hazard ratios were estimated using Cox regression, adjusted for potential confounding variables. RESULTS:The variant allele (298Asp) of the Glu298Asp SNP in the endothelial nitric oxide synthase gene (NOS3) was significantly associated with CKD after LT (P=.05; adjusted for multiple comparisons). The 5-year incidence of CKD was 70% among patients homozygous for the NOS3 variant allele (298Asp) compared with 42% among those not homozygous for the NOS3 variant allele. Specifically, homozygosity for the NOS3 variant allele conferred a 2.5-fold increased risk of developing CKD after LT (P=.005, adjusted for confounding variables). CONCLUSION:Homozygosity for the variant allele of NOS3 (298Asp) is associated with CKD after LT and may be useful for identifying recipients at higher risk of post-LT CKD. Proc. 2010;85(9):814-820 BMI = body mass index; CI = confidence interval; CKD = chronic kidney disease; CNI = calcineurin inhibitor; eGFR = estimated glomerular filtration rate; eNOS = endothelial nitric oxide synthase; GFR = glomerular filtration rate; HR = hazard ratio; LT = liver transplant; NO = nitric oxide; PCR = polymerase chain reaction; SNP = single nucleotide polymorphism Mayo Clin

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Genetic polymorphisms of adrenergic receptors

Cited by 14 publications

References 103 publications

Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-αvβ3 interactions

Epinephrine acts through erythroid signaling pathways to activate sickle cell adhesion to endothelium via LW-αvβ3 interactions

Adrenergic-β2 receptor polymorphism and athletic performance

Endothelial Nitric Oxide Synthase Gene Variation Associated With Chronic Kidney Disease After Liver Transplant

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