Beta2-adrenoceptor agonist

Allosteric ligands are promising drugs owing to their remote regulations of the orthosteric ligand signaling pathway. There are few allosteric ligands due to the lack of handy and efficacious method for the screening. Herein, we developed an affinity chromatographic method for allosteric ligand screening by immobilizing purified beta2 adrenoceptor (β2 -AR) onto macroporous silica gel by a two-point tethering method. The method relies on the occupation of the orthosteric site by an antagonist and the chelation of N-terminal His-tag of the receptor and Ni2+ coated on the gel...

OBJECTIVE: Several tissues produce and release interleukin-6 (IL-6) in response to beta2 -adrenergic stimulation with selective agonists (beta2 -agonists). Moreover, exercise stimulates muscle IL-6 production, but whether beta2 -agonists regulate skeletal muscle production and release of IL-6 in humans, in association with exercise remains to be clarified. Thus, we investigated leg IL-6 release in response to beta2 -agonist salbutamol in lean young men at rest and in recovery from resistance exercise...

Immobilized protein has advanced in many areas like drug discovery. While this field evolved rapidly over the last three decades, the immobilization platform for the G-protein-coupled receptor (GPCR) remains unpromising due to its instability under the relatively harsh conditions of current methodologies. Taking beta2 -adrenoceptor (β2 -AR) as an example, we presented here a general strategy for immobilization of GPCRs by combining the His6 -tag trap system, conformation-specific aptamer, and target binding induced DNA hybridization...

Treatment of obesity with repurposed or novel drugs is an expanding research field. One approach is to target beta2 -adrenergic receptors because they regulate the metabolism and phenotype of adipose and skeletal muscle tissue. Several observations support a role for the beta2 -adrenergic receptor in obesity. Specific human beta2 -adrenergic receptor polymorphisms are associated with body composition and obesity, for which the Gln27Glu polymorphism is associated with obesity, while the Arg16Gly polymorphism is associated with lean mass in men and the development of obesity in specific populations...

CONTENT: Exercise blunts the effect of beta2-agonist on peripheral glucose uptake and energy expenditure. Whether such attenuation extends into recovery is unknown. OBJECTIVE: To examine the effect of beta2-agonist on leg glucose uptake and metabolic rate in recovery from exercise. DESIGN: Using leg arteriovenous balance technique and analyses of thigh muscle biopsies, we investigated the effect of beta2-agonist (24 mg oral salbutamol) versus placebo on leg glucose, lactate, and oxygen exchange before, during, and 0...

Introduction: Beta2-adrenoceptors regulate proliferation of keratinocytes. Nitric oxide (NO) produced by keratinocytes through stimulation of nitric oxide synthase (NOS) mediates keratinocyte proliferation. Aim: In this study, the mechanism interaction β-ARs and NO production on keratinocyte will be explored, and the important for proliferation will be studied. Material and methods: To understand the relationship among β2-adrenoceptors, NO production and proliferation in keratinocytes, the experiment is divided to two parts...

OBJECTIVE: We aim to determine the effect of a fixed-dose combination (FDC) of tiotropium/olodaterol on Physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) in a real world setting. METHODS: COPD patients were prospectively enrolled to evaluate the effect of a FDC of tiotropium/olodaterol inhaler therapy via the Respimat® Soft Mist™ inhaler (SMI) on the physical functioning scale (PF-10), and the general condition of the patient as assessed by the physician (Physician's Global Evaluation, PGE), and the patient's satisfaction after 6 weeks of treatment...

AIM: There is an increasing awareness of the impact of age and sex on cardiovascular diseases. Differences in physiology are suspected. Beta-adrenoceptors (beta-AR) are an important drug target in cardiovascular disease and potential differences might have significant impact on the treatment of many patients. To investigate whether age and sex affects beta-AR function, we analyzed a large data set on beta-AR-induced inotropy in human atrial trabeculae. METHODS: We performed multivariable analysis of individual atrial contractility data from trabeculae obtained during heart surgery of patients in sinus rhythm (535 trabeculae from 165 patients)...

Inhaled beta2 -adrenoceptor agonists (beta2 -agonists) are among the most used substances in competitive sports. The 2020 Prohibited List issued by the World Anti-Doping Agency restricts use of all selective and non-selective beta2 -agonists in- and out- of competition with few exemptions. Formoterol, salbutamol, and salmeterol are allowed by inhalation within defined dosing limits. These restrictions are in place because supratherapeutic use of beta2 -agonist has the potential to be anabolic and to enhance performance, as well as due to potential side effects...

Clenbuterol is a beta2 -adrenoceptor agonist marketed as an asthma reliever but is not approved for human use in most countries due to concerns of adverse cardiac effects. Given its demonstrated hypertrophic and lipolytic actions in rodents, clenbuterol is one of the most widely abused doping substances amongt athletes and recreational body-builders seeking leanness. Herein, we examined the effect of clenbuterol ingestion on metabolic rate as well as skeletal muscle mammalian target of rapamycin (mTOR) phosphorylation and protein kinase A (PKA)-signaling in six young men...

The thyroid hormone metabolite 3-iodothyronamine (3-T1AM) exerts diverse physiological reactions such as a decrease of body temperature, and negative inotropic and chronotropic effects. This observed pleomorphic effect in physiology can be barely explained by interaction with only one target protein such as the trace-amine receptor 1 (TAAR1), a class A G-protein coupled receptor (GPCR). Moreover, Taar1 knock-out mice still react to 3-T1AM through physiological responses with a rapid decrease in body temperature...

While beta2 -adrenoceptor stimulation has been shown to increase lean mass and to alter metabolic properties of skeletal muscle, adaptations in muscle oxidative enzymes and maximal oxygen uptake (V̇O2max ) in response to beta2 -adrenergic agonist treatment are inadequately explored in humans, particularly in association with resistance training. Herein we investigated beta2 -adrenergic-induced changes in V̇O2max , leg and arm composition, and muscle content of oxidative enzymes in response to treatment with the selective beta2 -adrenergic agonist terbutaline with and without concurrent resistance training in young men...

AIM: To evaluate the therapeutic potential of ligands of beta-adrenoceptors in cognitive disorders. Testosterone and adrenergic pathways are involved in hippocampal and emotional memory. Moreover, is strongly suggested that androgen diminishing in aging is involved in cognitive deficit, as well as beta-adrenoceptors, particularly beta2-adrenoceptor, participate in the adrenergic modulation of memory. In this regard, some animal models of memory disruption have shown improved performance after beta-drug administration...

Formoterol is a long-acting beta2-adrenoceptor agonist (LABA) used for treatment of asthma and exercise-induced bronchoconstriction. Formoterol is usually administered as a racemic (rac-) mixture of (R,R)- and (S,S)-enantiomers. While formoterol is restricted by the World Anti-Doping Agency (WADA), inhalation of formoterol is permitted to a predetermined dose (54 μg/24 hours) and a urine threshold of 40 ng/mL. However, chiral switch enantiopure (R,R)-formoterol is available, effectively doubling the therapeutic advantage for the same threshold...

Evidence supporting the use of β2AR agonists in synucleinopathies is rapidly growing. Findings come from different scientific approaches. Molecular and immunological data suggest that adrenergic stimulation may decrease both α-synuclein (α-syn) deposition and pro-inflammatory/neurotoxic molecules release. Small open label clinical trials including a total number of 25 Parkinson's disease (PD) patients, in which the β2AR agonist salbutamol was added to levodopa, suggest a promising symptomatic benefit. In line with these findings, epidemiological studies investigating the risk of PD development suggest that long term exposure to the agonist salbutamol might be protective, while the antagonist propranolol possibly detrimental...

The design of beta2 adrenoceptor (β2 AR) agonists is attractive because of their wide-ranging applications in medicine, and the details of agonist interactions with β2 AR are interesting because it is considered a prototype for G-protein coupled receptors. Preclinical studies for agonist development have involved biological assays with guinea pigs due to a similar physiology to humans. Boron-containing Albuterol derivatives (BCADs) designed as bronchodilators have improved potency and efficacy compared with their boron-free precursor on guinea pig β2 ARs (gpβ2 ARs), and two of the BCADs (BR-AEA and boronterol) conserve these features on cells expressing human β2 ARs (hβ2 ARs)...

KEY POINTS: Animal models have shown that beta2 -adrenoceptor stimulation increases protein synthesis and attenuates breakdown processes in skeletal muscle. Thus, the beta2 -adrenoceptor is a potential target in the treatment of disuse-, disease- and age-related muscle atrophy. In the present study, we show that a few days of oral treatment with the commonly prescribed beta2 -adrenoceptor agonist, salbutamol, increased skeletal muscle protein synthesis and breakdown during the first 5 h after resistance exercise in young men...

First functional acting autoantibodies against G protein-coupled receptors such as the beta2-adrenoceptor in e.g. asthmatic patients have already been discovered in the early 1980s of the last century using assays that show their functional activity. Today, almost 40 years later, the measurement of such autoantibodies is still a challenge. Bioassays able to show the functional activity of such autoantibodies against G protein-coupled receptors are still the ne plus ultra for their detection and also classification when additionally exploiting specific receptor blockers for the neutralisation of the effect...

Due to a high prevalence of asthma and exercise-induced bronchoconstriction in elite athletes, there is a high use of beta2 -adrenoceptor agonists (beta2 -agonists) in the athletic population. While anabolic in rodents, no study has been able to detect hypertrophy in humans after chronic beta2 -agonist inhalation. We investigated whether inhaled beta2 -agonist, terbutaline, alters body composition and metabolic rate with and without concurrent exercise training in healthy young men. Sixty-seven participants completed a 4-week intervention of daily terbutaline (8 × 0...

KEY POINTS: While several studies have investigated the effects of exercise training in human skeletal muscle and the chronic effect of β2 -agonist treatment in rodent muscle, their effects on muscle proteome signature with related functional measures in humans are still incompletely understood. Herein we show that daily β2 -agonist treatment attenuates training-induced enhancements in exercise performance and maximal oxygen consumption, and alters muscle proteome signature and phenotype in trained young men...