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Beta3 adrenergic receptor

Jean-Luc Balligand
No abstract text is available yet for this article.
April 2017: European Journal of Heart Failure
Simona Negreş, Anca Zanfirescu, Floriana Elvira Ionică, Elena Moroşan, Bruno Ştefan Velescu, Oana Cristina Şeremet, Cristina Elena Zbârcea, Emil Ştefănescu, Manuella Militaru, Andreea LetiŢia Arsene, Denisa Marilena Margină, Livia Uncu, Corina Scutari, Cornel ChiriŢă
BACKGROUND AND AIMS: Beta3-adrenergic receptors (beta3-ARs) have been initially characterized in 1989. Afterwards, their tissue distribution was established: white and brown adipose tissue, central nervous system, myocardium (atrial and ventricular), blood vessels, smooth gastrointestinal muscles (stomach, small intestine, colon), gallbladder, urinary bladder, prostate, skeletal muscles. Non-clinical trials have demonstrated the major implication of beta3-ARs in glucose metabolism, implicitly, in insulin release, and also in obesity...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
Henning Bundgaard, Anna Axelsson, Jakob Hartvig Thomsen, Mathias Sørgaard, Klaus F Kofoed, Rasmus Hasselbalch, Natasha A S Fry, Nana Valeur, Søren Boesgaard, Finn Gustafsson, Lars Køber, Kasper Iversen, Helge H Rasmussen
AIMS: The third isotype of beta adrenergic receptors (β3 ARs) has distinctly different effects on cardiomyocytes compared with β1 and β2 ARs. Stimulation of β3 ARs may reduce cardiomyocyte Na(+) overload and reduce oxidative stress in heart failure (HF). We examined if treatment with the β3 AR agonist mirabegron increases LVEF in patients with HF. METHODS AND RESULTS: In a double-blind trial we randomly assigned 70 patients with NYHA class II-III HF and LVEF <40% at screening-echocardiography to receive mirabegron or placebo for 6 months as add-on to optimized standard therapy...
April 2017: European Journal of Heart Failure
Fabiane Ferreira Martins, Thereza Cristina Lonzetti Bargut, Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda
Brown adipose tissue (BAT) is specialized in heat production, but its metabolism in ob/ob mice is still a matter of debate. We aimed to verify ob/ob mice BAT using C57Bl/6 male mice (as the wild-type, WT) and leptin-deficient ob/ob mice (on the C57Bl/6 background strain), at three months of age (n=10/group). At euthanasia, animals had their interscapular BAT weighed, and prepared for analysis (Western blot, and RT-qPCR). In comparison with the WT group, the ob/ob group showed reduced thermogenic signaling markers (gene expression of beta 3-adrenergic receptor, beta3-AR; PPARgamma coactivator 1 alpha, PGC1alpha, and uncoupling protein 1, UCP1)...
March 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
Jerry Di Salvo, Hiroshi Nagabukuro, Alexandra Wickham, Catherine Abbadie, Julie A DeMartino, Aileen Fitzmaurice, Loise Gichuru, Alison Kulick, Marcie J Donnelly, Nina Jochnowitz, Amanda Hurley, Antonio Pereira, Anthony Sanfiz, Gregory Veronin, Katherine Villa, John Woods, Beata Zamlynny, Emanuel Zycband, Gino M Salituro, Tara Frenkl, Ann E Weber, Scott D Edmondson, Mary Struthers
Although the physiological role of muscarinic receptors in bladder function and the therapeutic efficacy of muscarinic antagonists for the treatment of overactive bladder are well established, the role of β3-adrenergic receptors (β3ARs) and their potential as therapeutics is just emerging. In this manuscript, we characterized the pharmacology of a novel β3AR agonist vibegron (MK-4618, KRP-114V) and explored mechanistic interactions of β3AR agonism and muscarinic antagonism in urinary bladder function. Vibegron is a potent, selective full β3AR agonist across species and it dose-dependently increased bladder capacity, decreased micturition pressure and increased bladder compliance in rhesus monkeys...
December 13, 2016: Journal of Pharmacology and Experimental Therapeutics
Nailliw Z Preite, Bruna P P do Nascimento, Cynthia R Muller, Anna Laura V Américo, Talita S Higa, Fabiana S Evangelista, Carmen L Lancellotti, Felipe dos Santos Henriques, Miguel Luiz Batista, Antonio C Bianco, Miriam O Ribeiro
The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system through β-adrenergic receptors (AR). Here, we wished to define the role played by the ARβ3 isoform in this process. This study focused on the ARβ3 knockout mice (ARβ3KO), including responsiveness to cold exposure, diet-induced obesity, intolerance to glucose, dyslipidaemia and lipolysis in white adipose tissue (WAT). ARβ3KO mice defend core temperature during cold exposure (4°C for 5 h), with faster BAT thermal response to norepinephrine (NE) infusion when compared with wild-type (WT) mice...
2016: Journal of Endocrinology
Heno F Lopes, Maria Lúcia Corrêa-Giannella, Fernanda M Consolim-Colombo, Brent M Egan
The association of anthropometric (waist circumference) and hemodynamic (blood pressure) changes with abnormalities in glucose and lipid metabolism has been motivation for a lot of discussions in the last 30 years. Nowadays, blood pressure, body mass index/abdominal circumference, glycemia, triglyceridemia, and HDL-cholesterol concentrations are considered in the definition of Metabolic syndrome, referred as Visceral adiposity syndrome (VAS) in the present review. However, more than 250 years ago an association between visceral and mediastinal obesity with hypertension, gout, and obstructive apnea had already been recognized...
2016: Diabetology & Metabolic Syndrome
Lubica Horvathova, Alexandra Padova, Andrej Tillinger, Jana Osacka, Jozef Bizik, Boris Mravec
Accumulated evidence indicates that sympathetic nerves may potentiate tumor growth, including melanoma. To elucidate possible mechanisms for this effect, we performed chemical sympathectomy by intraperitoneal (i.p.) injection of the neurotoxin 6-hydroxydopamine hydrobromide (100 mg/kg of body weight); in nine adult male C57BL/6J mice; nine control mice received i.p. vehicle (VEH). Seven days later, all mice were injected subcutaneously with 3 × 10(3) B16-F10 melanoma cells. Mice were euthanized 20 d after injection of melanoma cells, for measurement of tumor weight and expression of genes related to sympathetic signaling, apoptosis, hypoxia and angiogenesis in tumor tissue...
September 2016: Stress: the International Journal on the Biology of Stress
Jean-Luc Balligand
Overstimulation of the orthosympathetic system leads to cardiovascular cell and tissue damage through prolonged activation of β-1-2 adrenergic receptors (BARs). The more recent identification of the third isotype of BAR (B3AR) in cardiac myocytes and endothelial cells with a distinctive coupling and effect on cardiac function and remodelling introduced a new facet to this paradigm. In particular, B3AR is up-regulated in cardiac disease and less prone to homologous desensitization, which may reinforce its influence on the diseased myocardium...
July 15, 2016: Cardiovascular Research
China Chien, Hsi-Yang Wu
INTRODUCTION: Previous studies have suggested that the onset of alpha- (α) and beta- (β) adrenergic receptor activity is delayed in young animals. The use of alpha1- (α1-) antagonists for dysfunctional voiding, and beta3- (β3-) agonists for overactive bladder in younger children may not be indicated if maturation is required before bladder and urethral adrenergic receptors are active. OBJECTIVE: To determine the sex- and age-dependent responses of the bladder and external urethral sphincter (EUS) to α- and β-adrenergic agents in neonatal and young adult rats...
April 2016: Journal of Pediatric Urology
Hongyi Zhou, Xinnuo Lei, Tyler Benson, James Mintz, Xiaojing Xu, Ruth B Harris, Neal L Weintraub, Xiaoling Wang, Weiqin Chen
Mutations in BSCL2/SEIPIN cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), but the mechanisms whereby Bscl2 regulates adipose tissue function are unclear. Here, we generated adipose tissue (mature) Bscl2 knockout (Ad-mKO) mice, in which Bscl2 was specifically ablated in adipocytes of adult animals, to investigate the impact of acquired Bscl2 deletion on adipose tissue function and energy balance. Ad-mKO mice displayed reduced adiposity and were protected against high fat diet-induced obesity, but not insulin resistance or hepatic steatosis...
October 2015: Journal of Lipid Research
L H Petersen, M L Burleson, D B Huggett
β₃-adrenergic receptors (AR) are important in teleost cardiovascular regulation. To date, it is unknown whether temperature acclimation changes ß₃-AR functionality and consequently the involvement of this AR subtype in teleost cardiac regulation. Common carp (Cyprinus carpio) were acclimated at 12 °C or 23 °C (minimum 3 weeks) after which cardiovascular variables (cardiac output (Q), stroke volume (Sv) and heart rate (fH)) were measured upon injection of the ß₃-AR agonist, BRL(37344), and antagonist, SR(59230A)...
July 2015: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Robin Hertzberg, Guillermo Monreal Santiago, Christina Moberg
A novel methodology to produce highly enantioenriched N-(2-ethylamino)-β-amino alcohols was developed. These compounds were obtained from O-(α-bromoacyl) cyanohydrins, which were synthesized by the minor enantiomer methodology employing a Lewis acid and a biocatalyst, followed by nucleophilic substitution with amines and reduction. The importance of the developed methodology was demonstrated by completing a highly enantioselective total synthesis of the β3-adrenergic receptor agonist Solabegron.
March 6, 2015: Journal of Organic Chemistry
Nichola Thompson, Korinna Huber, Mirijam Bedürftig, Kathrin Hansen, Jennifer Miles-Chan, Bernhard H Breier
BACKGROUND: A number of different pathways to obesity with different metabolic outcomes are recognised. Prenatal undernutrition in rats leads to increased fat deposition in adulthood. However, the form of obesity is metabolically distinct from obesity induced through other pathways (e.g. diet-induced obesity). Previous rat studies have shown that maternal undernutrition during pregnancy led to insulin hyper-secretion and obesity in offspring, but not to systemic insulin resistance. Increased muscle and liver glycogen stores indicated that glucose is taken up efficiently, reflecting an active physiological function of these energy storage tissues...
2014: Nutrition & Metabolism
E Montaudon, M A Abdelkrim, J-C Desfontis, M Y Mallem
PURPOSE: To analyze vascular reactivity changes in response to immunization protocols with antigens corresponding to the second extracellular loop of -β3 and -β1 and 3 adrenergic receptors (AR). METHODS: Lewis rats were immunized for 3months with peptidic sequences corresponding to the second extracellular loop of β3-AR or β1 and 3-AR. Specific β3-AR antibodies were characterized by Elisa and purified using "Proteus Protein G" kit. Their functionality were tested in rabbit isolated ventricular cardiomyocytes...
June 2014: Annales de Cardiologie et D'angéiologie
Claudius Füllhase, Roberto Soler, Christian Gratzke
PURPOSE OF REVIEW: Improved understanding of the pathogenesis of lower urinary tract symptoms (LUTS) has led to the development of new drugs to treat male LUTS. The review aims to give an overview to the new drugs and to compounds in the pipeline. RECENT FINDINGS: Tadalafil, a phosphodiesterase type 5 inhibitor, is a drug newly approved for the treatment of male LUTS and a true new challenger for the current standard treatment with alpha1 blockers, particularly in men with concomitant erectile dysfunction...
January 2014: Current Opinion in Urology
Yan-Hui Gao, Hai-Bo Gao, Ning-Ning Di, Yi-Hui Kong, Wei-Min Li
OBJECTIVE: To observe the effects of beta3-adrenergic receptor(beta3-AR) antagonist on myocardial uncoupling protein 2 (UCP2) expression and energy metabolism in chronic heart failure rats. METHODS: Seven weight-matched normal adult rats (control group), 18 isoproterenol (ISO) induced heat failure (HR) rats (ISO group) and 21 ISO induced heart failure rats but received specific beta3-AR inhibitor SR59230A (ISO+ SR59230A group) for 6 weeks were included in this research...
July 2013: Chinese Journal of Applied Physiology
Pelin Tanyeri, Mehmet Emin Buyukokuroglu, Oguz Mutlu, Guner Ulak, Furuzan Yildiz Akar, Ipek Komsuoglu Celikyurt, Bekir Faruk Erden
Anxiety disorders are the most common behavioral disorders, and they exhibit high comorbidity rates. The aim of the present study was to confirm the effects of Amibegron, the first selective beta 3 adrenergic agent, on anxiety and to demonstrate that different serotoninergic receptor subtypes are involved in this effect. We administered the serotonin 5-HT1A receptor antagonist WAY-100635, the serotonin 5-HT2A receptor antagonist Ketanserin and the serotonin 5-HT3 receptor antagonist Ondansetron in mice and evaluated their performance in the elevated plus-maze test...
September 2013: Pharmacology, Biochemistry, and Behavior
Vabren L Watts, Fernando M Sepulveda, Oscar H Cingolani, Alice S Ho, Xiaolin Niu, Rosa Kim, Karen L Miller, Koenraad Vandegaer, Djahida Bedja, Kathleen L Gabrielson, Gerald Rameau, Brian O'Rourke, David A Kass, Lili A Barouch
RATIONALE: Stimulation of β3-adrenoreceptors (β3-AR) blunts contractility and improves chronic left ventricular function in hypertrophied and failing hearts in a neuronal nitric oxide synthase (nNOS) dependent manner. nNOS can be regulated by post-translational modification of stimulatory phosphorylation residue Ser1412 and inhibitory residue Ser847. However, the role of phosphorylation of these residues in cardiomyocytes and β3-AR protective signaling has yet to be explored. OBJECTIVE: We tested the hypothesis that β3-AR regulation of myocyte stress requires changes in nNOS activation mediated by differential nNOS phosphorylation...
September 2013: Journal of Molecular and Cellular Cardiology
Tarik Hadi, Marina Barrichon, Pascal Mourtialon, Maeva Wendremaire, Carmen Garrido, Paul Sagot, Marc Bardou, Frédéric Lirussi
The beta3 adrenergic receptor (B3-AR) reportedly induces cell proliferation, but the signaling pathways that were proposed, involving either Gs or Gi coupling, remain controversial. To further investigate the role of G protein coupling in B3-AR induced proliferation, we stimulated primary human myometrial smooth muscle cells with SAR150640 (B3-AR agonist) in the absence or presence of variable G-protein inhibitors. Specific B3-AR stimulation led to an Erk1/2 induced proliferation. We observed that the proliferative effects of B3-AR require two Erk1/2 activation peaks (the first after 3min, the second at 8h)...
May 2013: Biochimica et Biophysica Acta
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