Efficacy of Quercetin as a potent sensitizer of β2-AR in combating the impairment of fluid clearance in lungs of rats under hypoxia

• Published in: Respiratory physiology & neurobiology 2020-02, Vol.273, p.103334, Article 103334
• Main Authors: Tripathi, Ankit, Kumar, Manoj, Kaur, Punit, Kumar, Bhuvnesh, Sagi, Sarada S.K.
• Format: Article
• Language: English
• Subjects: Adrenergic beta-2 Receptor Agonists - administration & dosage; Adrenergic beta-2 Receptor Agonists - pharmacology; Albuterol - administration & dosage; Albuterol - pharmacology; Animals; Antioxidants - administration & dosage; Antioxidants - pharmacology; Body Fluids - drug effects; cAMP; Cyclic AMP-Dependent Protein Kinases - drug effects; Disease Models, Animal; Gene Expression - drug effects; Hypoxia; Hypoxia - drug therapy; Hypoxia - metabolism; Inflammation; Inflammation - drug therapy; Male; PKA; Pulmonary Alveoli - drug effects; Quercetin; Quercetin - administration & dosage; Quercetin - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta-2 - drug effects; Receptors, Adrenergic, beta-2 - metabolism; Signal Transduction - drug effects; Up-Regulation; β2-AR
• ISSN: 1569-9048; 1878-1519
• DOI: 10.1016/j.resp.2019.103334

•Acute hypoxia exposure (6h) desensitise the the β2 adrenergic receptors (β2 AR) present in the lungs of the rats.•Hypoxia mediated dysregulation of β2 AR resulted into the down regulation of Alveolar fluid clearance (AFC) in the lungs.•Increased production of reative oxygen species (ROS) as a result of hypoxia lead to the aberrant expression of Protein Kinase A (PKA) independent of cAMP levels.•Quercetin exhibited higher binding affinity towards β2 AR over salbutamol.•Prophylactic administration of quercetin resulted in the resensitization of β2 AR cascade and elevated the excess fluid clearance in the lungs. Hypoxia reportedly increases free radical generation in the body, causing oxidative stress and inhibiting β2-AR signaling. The present study correlates the prophylactic potential of quercetin and salbutamol in ameliorating fluid clearing capacity of lungs by re-sensitizing β2-AR signaling under hypoxia. Male SD rats supplemented orally with quercetin (50 mg/Kg BW), and salbutamol (2 mg/Kg BW) were exposed to hypobaric hypoxia at 7620 m for 6 h. Western blotting and ELISA quantitated NFĸB and related genes and GPCR pathway proteins. The binding affinities of drugs with receptor were determined by SPR spectroscopy and further confirmed insilico. Quercetin and salbutamol pre-treatment significantly up-regulated the expressions of β2-AR, GPR-1, GPR-10, GCSα, cAMP content, and down-regulated GRK-2, β-arrestin, ROS, NFκB (p