Disease relevance of Adrb2

• Here we show, by analysing Adrb2-deficient mice, that the sympathetic nervous system favours bone resorption by increasing expression in osteoblast progenitor cells of the osteoclast differentiation factor Rankl [1].
• In contrast, stimulation of beta2-AR exerts an anti-apoptotic effect which appears to be mediated by a pertussis toxin-sensitive G protein [2].
• Myocardial overexpression of beta2-AR at low levels results in improved cardiac function, whereas expression at high levels leads to dilated cardiomyopathy [2].
• We studied the effect of long term beta 2AR/Gs alpha activation on the growth rate of S49 lymphoma cells and carcinoma carB cells, a highly proliferative cancer cell line expressing oncogenic ras protein [3].
• Donor hearts received 1 ml of solution containing 1 x 1010 p.f.u. of adenovirus encoding the beta2-AR or an empty adenovirus as a control [4].

High impact information on Adrb2

• Axon guidance of mouse olfactory sensory neurons by odorant receptors and the beta2 adrenergic receptor [5].
• Using the hamster beta 2-adrenergic receptor gene as a hybridization probe we have isolated related genes including a cDNA encoding the rat D2 dopamine receptor [6].
• Enhanced myocardial relaxation in vivo in transgenic mice overexpressing the beta2-adrenergic receptor is associated with reduced phospholamban protein [7].
• Incubation of the transfected Y1 cells, which do not normally possess beta 2AR, with the beta 2AR agonist, isoproterenol, resulted in an increase in the rate of steroid secretion by these cells as well as a rapid change in cell morphology [8].
• This response was fully blocked by the beta 2AR antagonist, propranolol [8].

Chemical compound and disease context of Adrb2

• These studies demonstrated that isoproterenol enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells via beta 2-adrenergic receptor and cyclic AMP-dependent protein kinase pathways [9].
• RATIONALE: Salmeterol is a beta2-adrenoreceptor agonist used in the treatment of obstructive pulmonary disease [10].
• Therefore, the up-regulation of the beta 2-adrenergic receptor density and the temporal increase of the angiotensin I and II concentrations in the murine ventricle during viral myocarditis may play an important role in the pathophysiology of post-viral myocarditis [11].
• Therefore, it is suggested that a beta2-adrenergic receptor exists in the membranes of Ehrlich ascites tumor cells in terms of the adenylate cyclase-cAMP system [12].
• Skeletal muscle hypertrophy and anti-atrophy effects of clenbuterol are mediated by the beta2-adrenergic receptor [13].

Biological context of Adrb2

• Sympathetic signalling via beta2-adrenergic receptors (Adrb2) present on osteoblasts controls bone formation downstream of leptin [1].
• Beta -Arrestin 1 down-regulation after insulin treatment is associated with supersensitization of beta 2 adrenergic receptor Galpha s signaling in 3T3-L1 adipocytes [14].
• In summary, the primary physiologic consequences of the beta2-AR gene disruption are observed only during the stress of exercise and are the result of alterations in both vascular tone and energy metabolism [15].
• Despite this defect in vasodilation, beta2-AR -/- mice can still exercise normally and actually have a greater total exercise capacity than wild type mice [15].
• We searched public databases containing nucleotide sequences derived from mouse preimplantation cDNA libraries and found a partial sequence homology between a cDNA clone from mouse blastocysts and the mouse beta 2-adrenergic receptor sequence [16].

Anatomical context of Adrb2

• RESULTS: Western blots of rat heart nuclear fractions and confocal immunofluorescent analysis of adult rat and mouse ventricular cardiomyocytes displayed the presence of beta 1AR and beta 3AR but, surprisingly, not the beta 2AR on nuclear membranes [17].
• In conclusion, the differential cardioprotective/cardiotoxic effects mediated by beta1 vs. beta2-AR subtypes in knockout mice are recapitulated in myocytes isolated from these mice. beta2-ARs appear to play a cardioprotective role, whereas beta1-ARs a cardiotoxic role [18].
• Similarly, the beta2-adrenergic receptor (beta2-AR) was expressed on neurons and nerve fibers in the SMP of all species, as well as in the MP of the mouse [19].
• In the MP, beta1- and beta2-AR immunoreactivity was localized to several neuronal populations, including calretinin and nitrergic neurons [19].
• Using an antibody against the mouse beta 2-adrenergic receptor, we showed that the receptor protein is expressed in oocytes and preimplantation embryos; in blastocysts, the immufluorescence labeling was stronger in the inner cell mass than in throphectodermal cells [16].

Associations of Adrb2 with chemical compounds

• At comparable workloads, beta2-AR -/- mice had a lower respiratory exchange ratio than wild type mice suggesting a difference in energy metabolism. beta2-AR -/- mice become hypertensive during exercise and exhibit a greater hypertensive response to epinephrine compared with wild type mice [15].
• The regulation by dexamethasone of beta 1- and beta 2-adrenergic receptor expression during the adipose differentiation of 3T3-F442A cells was investigated at the receptor protein and mRNA level [20].
• Studies with CGP20712A or the beta 2AR-selective antagonist ICI118,551 indicated that this residual response was predominantly beta 2AR in character [21].
• Neither a beta 1AR-selective agonist, xamoterol, nor a beta 2AR-selective agonist, procaterol, was able to stimulate transcription [17].
• Isoproterenol response following transfection of the mouse beta 2-adrenergic receptor gene into Y1 cells [8].

Physical interactions of Adrb2

• In butyrate-exposed cells, proportions of beta-AR proteins and mRNAs were, respectively, 87 and 94% for beta 1 and 9 and 1% for beta 2-AR. beta 3-ARs were barely detectable in binding assays and accounted for 4.5% of beta-AR transcripts [22].
• The beta2-AR couples to Gs and Gi proteins [23].
• Phosphorylation of Try 350/354 creates a Src homology 2 (SH2) domain on the beta2-adrenergic receptor and the binding of adaptor protein Grb2 to this SH2 domain of the beta-adrenergic receptor takes place in an insulin-dependent manner [24].
• The J774 murine macrophage cells possess a beta 2-adrenergic receptor coupled to adenylate cyclase, which can be regulated by homologous desensitization [25].

Regulatory relationships of Adrb2

• beta-Arrestin 1 is required for internalization and mitogen-activated protein (MAP) kinase activation by the beta2 adrenergic receptor (beta2AR) [14].
• Importantly, beta 1 but not beta 2-AR mRNA levels up-regulated in white and brown adipose tissue of beta 3-AR-deficient mice (brown more than white), strongly implying that beta 3-ARs mediate physiologically relevant signaling under normal conditions and that "cross-talk" exists between beta 3-ARs and beta 1-AR gene expression [26].
• B cell receptor- and beta 2-adrenergic receptor-induced regulation of B7-2 (CD86) expression in B cells [27].
• The beta2-AR transgene construct was under the control of the murine alpha-myosin heavy chain (alpha-MHC) promoter, and ion channel activity was measured at distinct developmental stages using whole-cell and perforated patch clamp techniques [28].
• Noncanonical cAMP pathway and p38 MAPK mediate beta2-adrenergic receptor-induced IL-6 production in neonatal mouse cardiac fibroblasts [29].

Other interactions of Adrb2

• These findings occur despite persistent cardiac beta 2-AR expression, demonstrating the importance of beta 1-ARs for proper mouse development and cardiac function, while highlighting functional differences between beta-AR subtypes [30].
• Reverse transcriptase-PCR analysis showed that, in contrast to its dramatic down-regulatory effect on beta 3-AR mRNA, insulin did not modify the levels of beta 1- and beta 2-AR transcripts [31].
• That bone resorption cannot increase in gonadectomized Adrb2-deficient mice highlights the biological importance of this regulation, but also contrasts sharply with the increase in bone resorption characterizing another hypogonadic mouse with low sympathetic tone, the ob/ob mouse [1].
• Using RT-PCR, we showed that beta 2-adrenoceptor is transcribed not only at blastocyst stage but also at earlier stages of preimplantation development as well as in oocytes [16].
• We found that in Src-deficient cells the beta2-adrenergic receptor could activate the MAPK pathway [32].

Analytical, diagnostic and therapeutic context of Adrb2

• In order to define further the role of the different beta-AR subtypes, we have used gene targeting to inactivate selectively the beta2-AR gene in mice [15].
• In addition, GT1 cells express beta 1- but not beta 2-adrenergic receptor mRNA, as probed by Northern blot analysis [33].
• With oral administration, however, the effects of beta1-AR and beta2-AR can be different, depending on the species tested [34].
• Pulsed field gel electrophoresis has shown that the alpha 1- and beta 2-AR genes in humans are within 300 kilobases (kb) and the distance between the alpha 2- and beta 1-AR genes is less than 225 kb [35].
• In early anagen skin organ culture, the beta2-adrenoreceptor agonist isoproterenol promoted hair cycle progression from anagen III to anagen IV [36].

References