Upregulation of β
            <sub>3</sub>
            -Adrenoceptors and Altered Contractile Response to Inotropic Amines in Human Failing Myocardium

Moniotte, Stéphane; Kobzik, Lester; Féron, Olivier; Trochu, Jean‐Noël; Gauthier, Chantal; Balligand, Jean‐Luc

doi:10.1161/01.cir.103.12.1649

Cited by 302 publications

(303 citation statements)

References 30 publications

Supporting

Mentioning

270

Contrasting

Unclassified

Order By: Relevance

“…The function of ADRB3 in the heart includes increasing the contractility of myocardial tissue as indicated in studies of patients with heart failure (Moniotte et al, 2001;Morimoto et al, 2004) and dogs with pacing-induced heart failure (Cheng et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Distribution and quantification of β-3 adrenergic receptor in tissues of sheep

Liu

et al. 2011

Animal

View full text Add to dashboard Cite

The b-3 adrenergic receptor (ADRB3) is a G-protein coupled receptor involved in regulating lipolysis, as part of homeostatic regulation. In this study, South African Mutton Merino and Shanxi Dam Line were used to study the distribution and quantification of ADRB3 in adipose (subcutaneous, omental, retroperitoneal, mesenteric and perirenal fat) and non-adipose (heart, liver, spleen, lung and kidney) tissues of sheep. The protein was determined by immunohistochemical technique and by mRNA abundance via real-time polymerase chain reaction. ADRB3 was detected in all studied tissues with abundance in adipose tissues higher than in non-adipose tissues ( P , 0.001). For adipose tissues, greater expression was found in deep deposits such as great omental and retroperitoneal fat than in subcutaneous fat ( P , 0.05). Significant differences ( P , 0.05) both for mRNA and for protein expression also existed between the two sheep flocks. These findings are consistent with the known function of ADRB3 in mediating lipolysis and homeostasis in adipose tissues.Keywords: b-3 adrenergic receptor, sheep, tissues, mRNA expression, immunohistochemistry ImplicationsIn this study, the b-3 adrenergic receptor (ADRB3) expression in various tissues of sheep was detected by immunohistochemical technique and by mRNA abundance via real-time PCR. Despite its low expression, the presence of ADRB3 in the spleen and kidney was found in livestock for the first time. Generally, ADRB3 expressed higher in adipose than in non-adipose tissues, and for the former, it was higher in deep fat deposits than in subcutaneous fat. The distributions are consistent with the known functions of ADRB3 in mediating lipolysis and homeostasis in adipose tissues, and relaxation of vascular smooth muscle in the cardiovascular system. The relation between low expression and its function in some viscera, for example, lung, spleen and kidney of sheep deserves further study.Introduction b-Adrenergic receptors (ADRBs) are G-protein coupled receptors that mediate effects of the endogenous catecholamines adrenaline and noradrenaline. Three subtypes of ADRBs have been identified, named ADRB1, ADRB2 and ADRB3, respectively. These receptors are present in most mammalian tissues, but the distribution of each subtype varies among tissues in a given species. Among the various physiological roles of ADRBs, the ADRB3 subtype mediates lipolysis and stimulates thermogenesis in adipose tissues (Cannon and Nedergaard, 2004) by activating uncoupling protein in mitochondria.In early studies, ADRB3 was identified mainly on the surface of white and brown adipocytes as reviewed by Strosberg (1997). In recent years, expression of the protein was also found in the human heart (Rozec and Gauthier , (Rodriguez et al., 1995).It has been confirmed that the mRNA of the ADRB3 gene is expressed in various tissues of domestic animals. The 2.0 kb ADRB3 transcript in the bovine brown adipose tissue (PietriRouxel et al., 1995), and two transcripts of 2.2 and 1.9 kb in porcine subcutaneous fat (McNeel and ...

show abstract

Section: Discussionmentioning

confidence: 99%

Distribution and quantification of β-3 adrenergic receptor in tissues of sheep

Liu

et al. 2011

Animal

View full text Add to dashboard Cite

show abstract

“…It has been shown that b 2 -adrenoceptors, which are the main b-adrenoceptor subtype responsible for the vasodilator response induced by nonspecific b-agonists (O' Donnell & Wanstall, 1984), are less susceptible than b 1 -adrenoceptors to downregulation (Cohen & Schenck, 1987). In addition, b 3 -adrenoceptors can be upregulated when b 1 -and b 2 -adrenoceptor subtypes are downregulated (Rohrer et al, 1999;Moniotte et al, 2001). Moreover, it is known that high doses of ISO and other catecholamines can induce toxic effects (Balta et al, 1995;Banerjee et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Changes in vascular reactivity following administration of isoproterenol for 1 week: a role for endothelial modulation

Davel¹,

Kawamoto²,

Scavone³

et al. 2006

British J Pharmacology

View full text Add to dashboard Cite

1 The aim of this study was to assess the effects of treatment with isoproterenol (ISO, 0.3 mg kg À1 day À1 , s.c.) for 7 days on the vascular reactivity of rat-isolated aortic rings. Additionally, potential mechanisms underlying the changes that involved the endothelial modulation of contractility were investigated. 2 Treatment with ISO induced cardiac hypertrophy without changes in haemodynamic parameters. Aortic rings from ISO-treated rats showed an increase in the contraction response to phenylephrine (PHE) and serotonin, but did not change relaxations produced by acetylcholine or isoproterenol. Removal of the endothelium increased the responses to PHE in both groups. However, this procedure was less effective in ISO-treated as compared with control rats. Endothelial cell removal abolished the increase in the response to PHE in ISO-treated rats. The presence of N o -nitro-L-arginine methyl ester shifted the concentration-response curve to PHE to the left in both groups of rats. However, this effect was more pronounced in the ISO group. In addition, aminoguanidine (50 mM) potentiated the actions of PHE only in the ISO group. ISO treatment increased nitric oxide synthase (NOS) activity and neuronal NOS and endothelial NOS protein expression in the aorta. 3 Neither losartan (10 mM) nor indomethacin (10 mM) abolished the effects of ISO on the actions of PHE. Superoxide dismutase (SOD, 150 U ml À1 ) and L-arginine (5 mM), but neither catalase (300 U ml À1 ) nor apocynin (100 mM), blocked the effect of ISO treatment. In addition, we observed an increase in superoxide anion levels as measured by ethidium bromide fluorescence and of copper and zinc superoxide dismutase protein expression in ISO-treated rats. 4 In conclusion, our data suggest that ISO treatment alters the endothelial cell-mediated modulation of the contraction to PHE in rat aorta. The increased maximal response of PHE seems to be due to an increase in superoxide anion generation, which inactivates some of the basal NO produced and counteracts NO-mediated negative modulation even in the presence of high NO production and antioxidant defence.

show abstract

“…b 3 -Adrenoceptors stimulated by the preferential b 3 -adrenoceptor agonist BRL 37344 (BRL, ((RR þ SS)-(7)-4-[2-(2-(3-chlorophenyl)-2-hydroxyethyl)amino)propyl] phenoxyacetate)) induced a G i/o -protein dependent eNOS activation in the presence of nadolol (b 1 -/b 2 -adrenoceptor blockade) (Gauthier et al, 1998;Moniotte et al, 2001). Yet, the knowledge about the mechanisms resulting in an activation of eNOS in cardiomyocytes is limited (for a review, see Bloch et al, 2001a).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of β₃‐adrenoceptor‐induced eNOS activation in right atrial and left ventricular human myocardium

Brixius

Bloch

Pott

et al. 2004

British J Pharmacology

View full text Add to dashboard Cite

1 b-adrenoceptors are important modulators of cardiac function. The present study investigated b 3 -adrenergic eNOS activation in human myocardium. 2 We measured nitric oxide (NO) liberation (diaminofluorescence) and signal transduction (immunohistochemistry, phosphorylation of eNOS Ser1177 , eNOS Thr495 , eNOS Ser114 , Akt/protein kinase B (Akt/PKB), and eNOS translocation) in human right atrial (RA, aortocoronary-bypass OP) and left ventricular nonfailing (LV, rejected donor hearts) myocardium after application of BRL 37344 (BRL), a preferential b 3 -adrenoceptor agonist. 3 In both RA and LV, BRL (10 ml) induced a liberation of NO. An eNOS activation via translocation was only observed in RA after application of BRL (10 mM). Yet, the NO liberation in both LV and RA was accompanied by phosphorylation of eNOS Ser1177 and Akt/PKB. BRL-induced eNOS phosphorylation was abolished by LY292004, a blocker of PI-3 kinase. eNOS-Ser 114 phosphorylation was unchanged in RA, but decreased in LV after b 3 -adrenergic stimulation. BRL did not alter phosphorylation of eNOS Thr495 . 4 In conclusion, receptor-dependent eNOS activation is differentially regulated in the human heart. In the left ventricle, eNOS activation via phosphorylation seems to be of major importance, whereas in human atrial myocardium eNOS translocation is the predominant mechanism induced by b 3 -adrenergic activation.

show abstract

Upregulation of β ₃ -Adrenoceptors and Altered Contractile Response to Inotropic Amines in Human Failing Myocardium

Abstract: Opposite changes occur in beta(1)- and beta(3)-adrenoceptor abundance in the failing left ventricle, with an imbalance between their inotropic influences that may underlie the functional degradation of the human failing heart.

Cited by 302 publications

References 30 publications

Distribution and quantification of β-3 adrenergic receptor in tissues of sheep

Distribution and quantification of β-3 adrenergic receptor in tissues of sheep

Changes in vascular reactivity following administration of isoproterenol for 1 week: a role for endothelial modulation

Mechanisms of β₃‐adrenoceptor‐induced eNOS activation in right atrial and left ventricular human myocardium

Contact Info

Product

Resources

About

Upregulation of β 3 -Adrenoceptors and Altered Contractile Response to Inotropic Amines in Human Failing Myocardium

Abstract: Opposite changes occur in beta(1)- and beta(3)-adrenoceptor abundance in the failing left ventricle, with an imbalance between their inotropic influences that may underlie the functional degradation of the human failing heart.

Cited by 302 publications

References 30 publications

Distribution and quantification of β-3 adrenergic receptor in tissues of sheep

Distribution and quantification of β-3 adrenergic receptor in tissues of sheep

Changes in vascular reactivity following administration of isoproterenol for 1 week: a role for endothelial modulation

Mechanisms of β3‐adrenoceptor‐induced eNOS activation in right atrial and left ventricular human myocardium

Contact Info

Product

Resources

About

Upregulation of β ₃ -Adrenoceptors and Altered Contractile Response to Inotropic Amines in Human Failing Myocardium

Mechanisms of β₃‐adrenoceptor‐induced eNOS activation in right atrial and left ventricular human myocardium