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Beta1 adrenoceptor

Ewan D Fowler, Mark J Drinkhill, Ruth Norman, Eleftheria Pervolaraki, Rachel Stones, Emma Steer, David Benoist, Derek S Steele, Sarah C Calaghan, Ed White
Right heart failure is the major cause of death in Pulmonary Artery Hypertension (PAH) patients but is not a current, specific therapeutic target. Pre-clinical studies have shown that adrenoceptor blockade can improve cardiac function but the mechanisms of action within right ventricular (RV) myocytes are unknown. We tested whether the β1 -adrenoceptor blocker metoprolol could improve RV myocyte function in an animal model of PAH, by attenuating adverse excitation-contraction coupling remodeling. PAH with RV failure was induced in rats by monocrotaline injection...
May 26, 2018: Journal of Molecular and Cellular Cardiology
Justus Stenzig, Yvonne Schneeberger, Alexandra Löser, Barbara S Peters, Andreas Schaefer, Rong-Rong Zhao, Shi Ling Ng, Grit Höppner, Birgit Geertz, Marc N Hirt, Wilson Tan, Eleanor Wong, Hermann Reichenspurner, Roger S-Y Foo, Thomas Eschenhagen
BACKGROUND: Heart failure is associated with altered gene expression and DNA methylation. De novo DNA methylation is associated with gene silencing, but its role in cardiac pathology remains incompletely understood. We hypothesized that inhibition of DNA methyltransferases (DNMT) might prevent the deregulation of gene expression and the deterioration of cardiac function under pressure overload (PO). To test this hypothesis, we evaluated a DNMT inhibitor in PO in rats and analysed DNA methylation in cardiomyocytes...
May 21, 2018: Journal of Molecular and Cellular Cardiology
Valerie Boivin-Jahns, Roland Jahns, Fritz Boege
Patients suffering from chronic heart failure (CHF) caused or promoted by autoantibodies against cardiac beta1 -adrenergic receptors (beta1 AR) could benefit from specific therapies aimed at tolerance induction, removal or neutralisation of beta1 AR autoantibodies, provided the patients can be selected for these therapies by reliable detection and quantitation of beta1 AR autoantibodies in their circulation and by a valid assessment of the autoantibodies's putative cardio-pathogenic potential. Here, we discuss the current state of knowledge regarding the effects of CHF-associated (auto)antibodies on beta1 AR function and beta1 AR-mediated signal tranduction and discuss the presumed role of these effects in the development and progression of CHF...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
Tina Markus, David Ley, Stefan R Hansson, Tadeusz Wieloch, Karsten Ruscher
BACKGROUND: Labor subjects the fetus to an hypoxic episode and concomitant adrenomodullary catecholamine surge that may provide protection against the hypoxic insult. The beta1-adrenergic agonist dobutamine protects against hypoxia/aglycemia induced neuronal damage. We aimed to identify the associated protective biological processes involved. RESULTS: Hippocampal slices from 6 days old mice showed significant changes of gene expression comparing slices with or without dobutamine (50 mM) in the following two experimental paradigms: (1) control conditions versus lipopolysacharide (LPS) stimulation and (2) oxygen-glucose deprivation (OGD), versus combined LPS/OGD...
March 9, 2018: BMC Neuroscience
Katrin Wenzel, Sarah Schulze-Rothe, Johannes Müller, Gerd Wallukat, Annekathrin Haberland
Cell-based analytics for the detection of the beta1-adrenoceptor autoantibody (beta1-AAB) are functional, yet difficult to handle, and should be replaced by easily applicable, routine lab methods. Endeavors to develop solid-phase-based assays such as ELISA to exploit epitope moieties for trapping autoantibodies are ongoing. These solid-phase-based assays, however, are often unreliable when used with human patient material, in contrast to animal derived autoantibodies. We therefore tested an immunogen peptide-based ELISA for the detection of beta1-AAB, and compared commercially available goat antibodies against the 2nd extracellular loop of human beta1-adrenoceptor (ADRB1-AB) to autoantibodies enriched from patient material...
2018: PloS One
Liisa Ailanen, Suvi T Ruohonen, Laura H Vähätalo, Katja Tuomainen, Kim Eerola, Henriikka Salomäki-Myftari, Matias Röyttä, Asta Laiho, Markku Ahotupa, Helena Gylling, Eriika Savontaus
A gain-of-function polymorphism in human neuropeptide Y (NPY) gene (rs16139) associates with metabolic disorders and earlier onset of type 2 diabetes (T2D). Similarly, mice overexpressing NPY in noradrenergic neurons (OE-NPY(DBH)) display obesity and impaired glucose metabolism. In this study, the metabolic syndrome-like phenotype was characterized and mechanisms of impaired hepatic fatty acid, cholesterol and glucose metabolism in pre-obese (2-month-old) and obese (4-7-month-old) OE-NPY(DBH) mice were elucidated...
July 2017: Journal of Endocrinology
Yuhichi Kuda, Toshishige Shibamoto, Wei Yang, Tao Zhang, Mamoru Tanida, Yasutaka Kurata
BACKGROUND: Cardiac anaphylaxis is one of the features of anaphylactic hypotension. Patients treated with propranolol, a nonselective b-adrenoceptor (AR) antagonist, develop severe anaphylaxis, but the mechanism remains unknown. Under examination were the effects of b₁- and b₂-AR antagonist on anaphylaxis-induced coronary vasoconstriction and cardiac dysfunction in isolated blood-perfused rat hearts. METHODS: Isolated hearts from ovalbumin-sensitized Wistar rats were subjected to coronary perfusion with blood at a constant pressure and measurements were made of coronary blood flow and left ventricular (LV) pressure...
March 29, 2017: Cardiology Journal
Shivanjali Joshi-Barr, Annekathrin Haberland, Sabine Bartel, Johannes Müller, Ted Choi, Gerd Wallukat
BACKGROUND: While the involvement of adrenergic beta1-autoantibodies (beta1-AABs) in pathogenesis of cardiomyopathies is well established as are the benefits associated with autoantibody removal by immunoapheresis, the development of drugs neutralizing beta1-AABs in-vivo has been slowed due to a lack of high throughput autoantibody analytics. Highly scalable routine diagnostics involving immobilized binding partners have mostly failed in comparison to the laborious bioassays, which are difficult to scale up, but present the most reliable and sensitive tools for detecting the beta1-autoantibodies...
September 15, 2016: International Journal of Cardiology
Ye Miao, Hui Chen, Min Li
Beta1-adrenoreceptor (β1-AR) predominantly exists in the heart and β1-AR reduction is closely related to severity of heart failure (HF). In this study, our research focused on the miRNAs that may repress β1-AR directly, and aim to find out new markers and target molecules for HF. We first did Argonaute2 AGO2 knock down experiments and confirmed that endogenous adrenoceptor beta 1 (ADRB1) expression was suppressed by miRNAs. To further identify which miRNA suppress ADRB1 expression directly, we constructed the ADRB1 3'UTR reporter plasmid and selected sixteen candidate miRNAs...
2015: International Journal of Clinical and Experimental Medicine
Nana Zhang, Xiujing Sun, Mingjiong Sun, Shengtao Zhu, Li Wang, Dan Ma, Yongjun Wang, Shutian Zhang, Peng Li
Cigarette smoke is a risk factor for esophageal squamous cell carcinoma (ESCC). It contains several carcinogens known to initiate and promote tumorigenesis as well as metastasis. The nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the strongest carcinogens in tobacco and our previous studies have shown its proliferation-promoting role in the progression of ESCC. Recently, NNK was identified as an agonist for both beta1- and beta2-adrenoceptors. Thus, we hypothesized that the cancer-promoting effect of NNK was likely mediated through beta-adrenoceptors in ESCC...
2015: PloS One
Andrea Ahles, Fabian Rodewald, Francesca Rochais, Moritz Bünemann, Stefan Engelhardt
G protein-coupled receptors represent the largest class of drug targets, but genetic variation within G protein-coupled receptors leads to variable drug responses and, thereby, compromises their therapeutic application. One of the most intensely studied examples is a hyperfunctional variant of the human β1-adrenoceptor that carries an arginine at position 389 in helix 8 (Arg-389-ADRB1). However, the mechanism underlying the higher efficacy of the Arg-389 variant remained unclear to date. Despite its hyperfunctionality, we found the Arg-389 variant of ADRB1 to be hyperphosphorylated upon continuous stimulation with norepinephrine compared with the Gly-389 variant...
January 16, 2015: Journal of Biological Chemistry
O Hamzaoui, J L Teboul
β-blockers are widely used to treat cardiovascular diseases and in the peri-operative period in selected patients. The main benefit in terms of morbidity and/or mortality of their use is believed to be linked to specific effects on myocardial oxygen supply/demand balance, to anti-arrhythmic effects and anti-inflammatory effects. Use of β-blockers in severe sepsis is still under debate and if any, their appropriate indications remain unclear. In this article, we analyze the recent literature addressing the metabolic, immuno-modulatory and hemodynamic effects of non cardio-selective and of cardio-selective β-blockers in experimental and human sepsis in order to help clarifying the potential place of these drugs in patients with severe sepsis...
March 2015: Minerva Anestesiologica
Xia Li, Jun-Hong Gao, Xiao-Chun Yu, Yu-Xue Zhao, Jing-Jun Zhao, Bing Zhu, Pei-Jing Rong
OBJECTIVE: To observe the cardioprotective effect of electroacupuncture (EA) stimulation at "Neiguan" (PC 6) in mice with myocardial ischemia (MI) and to explore the involvement of cardiac beta-adrenergic receptors (beta-AR) in the cardioprotective effect of EA intervention. METHODS: Adult male C 57 BL/6 mice of wild type and beta1/beta2-AR double-knockout (beta1/beta2-AR(-/-)) mice were randomly and respectively divided into control group and EA group, with 8 mice in each group...
April 2014: Zhen Ci Yan Jiu, Acupuncture Research
Jin O-Uchi, Kimiaki Komukai, Yoichiro Kusakari, Satoshi Morimoto, Makoto Kawai, Bong Sook Jhun, Stephen Hurst, Kenichi Hongo, Shey-Shing Sheu, Satoshi Kurihara
Adrenoceptor stimulation is a key determinant of cardiac excitation-contraction coupling mainly through the activation of serine/threonine kinases. However, little is known about the role of protein tyrosine kinases (PTKs) activated by adrenergic signaling on cardiac excitation-contraction coupling. A cytoplasmic tyrosine residue in β1-adrenoceptor is estimated to regulate Gs-protein binding affinity from crystal structure studies, but the signaling pathway leading to the phosphorylation of these residues is unknown...
April 5, 2013: Biochemical and Biophysical Research Communications
Julia Gorelik, Peter T Wright, Alexander R Lyon, Sian E Harding
The beta1-adrenoceptors (β(1)AR) and beta-2 (β(2)AR) adrenoceptors represent the predominant pathway for sympathetic control of myocardial function. Diverse mechanisms have evolved to translate signalling via these two molecules into differential effects on physiology. In this review, we discuss how the functions of the βAR are organized from the level of secondary messengers to the whole heart to achieve this. Using novel microscopy and bio-imaging methods researchers have uncovered subtle organization of the control of cyclic adenosine monophosphate (cAMP), the predominant positively inotropic pathway for the βAR...
May 1, 2013: Cardiovascular Research
Mei-Ping Li, Guo-Jie Sun, Xing-Hong You
OBJECTIVE: To explore the mechanism of electroacupuncture (EA) of scalp-point in the management of myocardial ischemia-reperfusion injury (MI/RI) by examining its effects on left cardiac sympathetic nerve activity, myocardial beta1-adrenaline receptor (AR) protein expression and plasma norepinephrine (NE) concentration in MI/RI rats. METHODS: Eighteen Wistar rats were randomly divided into sham, model and EA groups (n = 6). MI/RI model was induced by ligation of the left anterior descending coronary artery for 30 min, followed by release of the ligation for 15 min...
October 2012: Zhen Ci Yan Jiu, Acupuncture Research
Thomas J Zieziulewicz, Tapan K Mondal, Donghong Gao, David A Lawrence
Acute cold restraint stress (ACRS) has been reported to suppress host defenses against Listeria monocytogenes, and this suppression was mediated by beta1-adrenoceptors (β1-ARs). Although ACRS appears to inhibit mainly early innate immune defenses, interference with leukocyte chemotaxis and the involvement of β1-AR (or β2-AR) signaling had not been assessed. Thus, the link between sympathetic nerve stimulation, release of neurotransmitters, and changes in blood leukocyte profiles, including oxidative changes, following ACRS was evaluated...
May 2013: Cell Stress & Chaperones
M A Abdelkrim, J Noireaud, G Chatagnon, M Gogny, J-C Desfontis, M Y Mallem
PURPOSE: To evaluate the effect of active immunization with a peptide corresponding to the second extracellular loop of the human beta1-adrenoceptors (β(1)-AR) on the reactivity of Wistar rat isolated aorta. METHODS: Nine-week-old Wistar rats were actively immunized for 3months with a peptide corresponding to the second extracellular loop of the human β(1)-AR. Specific immunoglobulins G (IgG) were characterized by Elisa and the bicinchonic acid protein assay and their functionality were tested in isolated ventricular cardiomyocytes (IVC) from control rats...
June 2012: Annales de Cardiologie et D'angéiologie
Meili Lu, Hongxin Wang, Yuhong Yang, Lei Zhang, Chunna Liu, Jing Yang, Tak Ming Wong
The aim of the present study, performed in an in vitro model of cardiac hypertrophy, was to examine the possible function of calcineurin and ERK1/2 in the inhibitory effects of kappa-opioid receptor stimulation on Ca2+ transients and myocardial hypertrophy induced by beta1-adrenoceptor stimulation. We determined the effects of trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamid methanesulfonate salt (U50,488H), a selective kappa-opioid receptor agonist, on the enhancement of spontaneous Ca2+ transients and the induction of hypertrophy by isoprenaline, a beta-adrenoceptor agonist, in cultured neonatal ventricular myocytes...
February 2012: Die Pharmazie
Ya-jie Li, Ni Li, Lin Yang, Yong-wang Li, Xu Ding, Hong-tao Zhao, Ying Li
OBJECTIVE: To evaluate the associations between polymorphisms Arg389Gly of β1-adrenergic receptor gene and essential hypertension risk. METHODS: "Hypertension", "polymorphism", "Arg389Gly" and "beta1-adrenergic" or "beta1-adrenoceptor" were used as key words to search the relevant publications between January 1990 and June 2011 in the databases of Pubmed, CNKI and Wanfang. Additional references cited in the retrieved articles were also evaluated. Between-study heterogeneity test was performed by the χ(2)-based Q test...
November 29, 2011: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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