β2-ar agonists  (Cowen Inc)

Journal: GeroScience

Article Title: Cell therapy rescues aging-induced beta-1 adrenergic receptor and GRK2 dysfunction in the coronary microcirculation

doi: 10.1007/s11357-021-00455-6

Figure Lengend Snippet: Expression of myocardial β1- and β2-AR with aging and following SVF therapy. Myocardial β1-AR protein expression is reduced (albeit not significantly) in aging and not reversed by SVF therapy. There is no significant change in myocardial β2-AR protein expression with age or with SVF therapy. Protein quantification for expression is measured by band intensity normalized to GAPDH, and data is presented as means ± SEM. Significance was determined by one-way ANOVA with Holm-Sidak post hoc analysis

Article Snippet: The drug/inhibitor protocols were randomized to the isolated vessels: Protocol 1 —BRL-37344 (β3-AR agonist, Sigma B169), norepinephrine (NE) (α1-2 and β1-2 AR agonist, Sigma-Aldrich A9512), and NE following 30 min of incubation with paroxetine HCl (NE + Parox) (GRK-selective antagonist, VWR 89160-896) and sodium fluoride (NaF) (Gs activator, Sigma-Aldrich S6776) Protocol 2 —NE, NE following 20 min of incubation with CPG20712A (NE + CPG) (β1-AR antagonist, Sigma C231) and forskolin (AC activator, VWR 89156-986) Protocol 3 —dobutamine (Dob) (primarily a β1-AR agonist with lower β2-AR activity, Sigma-Aldrich D0676), NE, Dob following 20 min of incubation with ICI118551 (Dob + ICI) (β2-AR antagonist, Sigma I127), NE + ICI, and 8-bromo-cAMP (cAMP-dependent protein kinase activator, VWR 89157-000) At the end of the protocol, the arterioles were washed 2 × 15 min in calcium-free PSS followed by a single high dose of sodium nitroprusside (SNP 1e −4 [M]) at the end of the experiment.

Techniques: Expressing

Journal: GeroScience

Article Title: Cell therapy rescues aging-induced beta-1 adrenergic receptor and GRK2 dysfunction in the coronary microcirculation

doi: 10.1007/s11357-021-00455-6

Figure Lengend Snippet: Immunofluorescence detection of adrenergic receptors in coronary microvessels. In coronary microvessels, the β1-AR is significantly reduced in aging and reversed to youthful levels by SVF therapy as measured by mean fluorescence intensity (arbitrary units) while β2-3 ARs and α1-2 ARs remain unchanged (a, b). Data is presented as means ± SEM, n’s are above the corresponding bars, and significance was determined by one-way ANOVA with Bonferroni post hoc testing, p ≤ .05 vs. YC (*) and vs. OC (#). ROI boxes are 10 × 100 μm. The scale bar equals 100 μm for the β-AR panels and 50 μm α-AR panels

Article Snippet: The drug/inhibitor protocols were randomized to the isolated vessels: Protocol 1 —BRL-37344 (β3-AR agonist, Sigma B169), norepinephrine (NE) (α1-2 and β1-2 AR agonist, Sigma-Aldrich A9512), and NE following 30 min of incubation with paroxetine HCl (NE + Parox) (GRK-selective antagonist, VWR 89160-896) and sodium fluoride (NaF) (Gs activator, Sigma-Aldrich S6776) Protocol 2 —NE, NE following 20 min of incubation with CPG20712A (NE + CPG) (β1-AR antagonist, Sigma C231) and forskolin (AC activator, VWR 89156-986) Protocol 3 —dobutamine (Dob) (primarily a β1-AR agonist with lower β2-AR activity, Sigma-Aldrich D0676), NE, Dob following 20 min of incubation with ICI118551 (Dob + ICI) (β2-AR antagonist, Sigma I127), NE + ICI, and 8-bromo-cAMP (cAMP-dependent protein kinase activator, VWR 89157-000) At the end of the protocol, the arterioles were washed 2 × 15 min in calcium-free PSS followed by a single high dose of sodium nitroprusside (SNP 1e −4 [M]) at the end of the experiment.

Techniques: Immunofluorescence, Fluorescence

Journal: GeroScience

Article Title: Cell therapy rescues aging-induced beta-1 adrenergic receptor and GRK2 dysfunction in the coronary microcirculation

doi: 10.1007/s11357-021-00455-6

Figure Lengend Snippet: Summary of adrenergic signaling with alterations due to aging and SVF therapy. In an aged coronary microvessel, there is a decrease in the β1-AR populations and vasodilation to β1-AR agonists is reduced. Adrenergic signaling is inhibited through GRK2 and Gαi proteins which are significantly increased in the aged myocardium and marginally increased in coronary microvessels. SVF cell therapy restores some vasodilatory capacity via rescuing β1-AR populations through post-translational modifications of GRK2 and the receptor recycling proteins beta-arrestins, as well as diminution in Gαi proteins. Green text represents activators whereas red text represents inhibitors. The thicker arrow pointing from NE to the β-ARs indicates higher antagonism toward β1-AR compared to β2-AR. Solid black arrows indicate positive effects of cell signaling while dashed lines indicate negative or inhibitory effects. A key and a summary of findings are shown to the right. Image created with BioRender.com

Article Snippet: The drug/inhibitor protocols were randomized to the isolated vessels: Protocol 1 —BRL-37344 (β3-AR agonist, Sigma B169), norepinephrine (NE) (α1-2 and β1-2 AR agonist, Sigma-Aldrich A9512), and NE following 30 min of incubation with paroxetine HCl (NE + Parox) (GRK-selective antagonist, VWR 89160-896) and sodium fluoride (NaF) (Gs activator, Sigma-Aldrich S6776) Protocol 2 —NE, NE following 20 min of incubation with CPG20712A (NE + CPG) (β1-AR antagonist, Sigma C231) and forskolin (AC activator, VWR 89156-986) Protocol 3 —dobutamine (Dob) (primarily a β1-AR agonist with lower β2-AR activity, Sigma-Aldrich D0676), NE, Dob following 20 min of incubation with ICI118551 (Dob + ICI) (β2-AR antagonist, Sigma I127), NE + ICI, and 8-bromo-cAMP (cAMP-dependent protein kinase activator, VWR 89157-000) At the end of the protocol, the arterioles were washed 2 × 15 min in calcium-free PSS followed by a single high dose of sodium nitroprusside (SNP 1e −4 [M]) at the end of the experiment.

Techniques:

Journal: The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology

Article Title: Deletion of adipose triglyceride lipase abolishes blood flow increase after β3-adrenergic stimulation in visceral adipose tissue of mice

doi: 10.4196/kjpp.2021.25.4.355

Figure Lengend Snippet: β-adrenergic receptor subtypes on the regulation of visceral adipose tissue blood flow (VAT BF) in CD-1 mice. (A) Experimental timeline diagram. After stabilizing VAT BF for 5 min, vehicle and agonists (10 –4 and 10 –2 M) were infused into VAT a rate of 0.5 µl min –1 for 10 min, respectively. Arrows represent the time point of the switch in the agonist delivery. (B) Changes in VAT BF induced by stimulation of dobutamine, a selective β1-adrenergic receptor agonist. (C) Changes in VAT BF induced by stimulation of salbutamol, a selective β2-adrenergic receptor agonist. (D) Changes in VAT BF induced by stimulation of CL316,243, a selective β3-adrenergic receptor agonist. *p < 0.05.

Article Snippet: After one week of acclimatization, the mice were randomly divided into three groups to monitor changes in VAT BF during local infusion of selective β1-AR agonist (dobutamine, D0676; Sigma-Aldrich, St Louis, MO, USA), selective β2-AR agonist (salbutamol, S8260; Sigma-Aldrich), and selective β3-AR agonist (CL316,243, C5976; Sigma-Aldrich) into VAT.

Techniques:

Journal: Nutrients

Article Title: Obesity Affects β2 Adrenergic Regulation of the Inflammatory Profile and Phenotype of Circulating Monocytes from Exercised Animals

doi: 10.3390/nu11112630

Figure Lengend Snippet: Effect of exercise on β2 adrenergic regulation of monocytes expressing pro-inflammatory cytokines (MCP-1, TNF-α, IL-8, IL-6) and pro-inflammatory phenotype (Ly6C, iNOS) in lean (sedentary n = 9; acute exercise n = 5; regular exercise n = 6) and obese mice (sedentary n = 8; acute exercise n = 5; regular exercise n = 6). Data are expressed as percentage change from baseline after β2 adrenergic stimulation with terbutaline (giving “100” to the basal values in the absence of terbutaline): ( A , B ): MCP-1+ cells in lean and obese mice, respectively. ( C , D ): TNF-α+ cells in lean and obese mice, respectively. ( E , F ): IL-8+ cells in lean and obese mice, respectively. ( G , H ): IL-6+ cells in lean and obese mice, respectively. ( I , J ): Ly6C+ cells in lean and obese mice, respectively. ( K , L ): iNOS+ cells in lean and obese mice, respectively. Columns show the mean ± SEM of independent assays performed in duplicate in each animal. * p < 0.05, ** p < 0.01 vs. the corresponding sedentary mice group.

Article Snippet: Cells were cultured with brefeldin A solution (1 μg/mL) (Thermo Fisher Scientific, Waltham, MA, USA), a protein transport inhibitor for the enhancement of the intracellular staining of cytokines, in the presence or absence of the selective β2 AR agonist terbutaline (1 μM) (Sigma-Aldrich, St. Louis, MO, USA).

Techniques: Expressing

Journal: Nutrients

Article Title: Obesity Affects β2 Adrenergic Regulation of the Inflammatory Profile and Phenotype of Circulating Monocytes from Exercised Animals

doi: 10.3390/nu11112630

Figure Lengend Snippet: Effect of exercise on β2 adrenergic regulation of monocytes expressing anti-inflammatory cytokines (IL-10, TGF-β) and anti-inflammatory phenotype (ARG-1) in lean (sedentary n = 9; acute exercise n = 5; regular exercise n = 6) and obese mice (sedentary n = 8; acute exercise n = 5; regular exercise n = 6). Data are expressed as percentage change from baseline after β2 adrenergic stimulation with terbutaline (giving “100” to the basal values in the absence of terbutaline): ( A , B ): IL-10+ cells in lean and obese mice, respectively. ( C , D ): TGF-β+ cells in lean and obese mice, respectively. ( E , F ): ARG-1+ cells in lean and obese mice, respectively. Columns show the mean ± SEM of independent assays performed in duplicate in each animal. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. the corresponding sedentary mice group.

Article Snippet: Cells were cultured with brefeldin A solution (1 μg/mL) (Thermo Fisher Scientific, Waltham, MA, USA), a protein transport inhibitor for the enhancement of the intracellular staining of cytokines, in the presence or absence of the selective β2 AR agonist terbutaline (1 μM) (Sigma-Aldrich, St. Louis, MO, USA).

Techniques: Expressing