دورية أكاديمية

The Bronchoprotective Effects of Dual Pharmacology, Muscarinic Receptor Antagonist and β 2 Adrenergic Receptor Agonist Navafenterol in Human Small Airways.

التفاصيل البيبلوغرافية
العنوان: The Bronchoprotective Effects of Dual Pharmacology, Muscarinic Receptor Antagonist and β 2 Adrenergic Receptor Agonist Navafenterol in Human Small Airways.
المؤلفون: Jude, Joseph Antony, Dainty, Ian, Karmacharya, Nikhil, Jester, William, Panettieri, Reynold
المصدر: Cells (2073-4409); Jan2023, Vol. 12 Issue 2, p240, 8p
مصطلحات موضوعية: ADRENERGIC agonists, MUSCARINIC antagonists, MUSCARINIC receptors, CHRONIC obstructive pulmonary disease, LUNGS, MUSCARINIC agonists, PHARMACOLOGY, ALPHA adrenoceptors
مستخلص: Bronchodilators and anti-inflammatory agents are the mainstream treatments in chronic obstructive and pulmonary disease (COPD) and asthma. The combination of β2 adrenergic receptor (β2AR) agonists and muscarinic antagonists shows superior bronchoprotective effects compared to these agents individually. Navafenterol (AZD8871) is a single-molecule, dual pharmacology agent combining muscarinic antagonist and β2AR agonist functions, currently in development as a COPD therapeutic. In precision-cut human lung slices (hPCLS), we investigated the bronchoprotective effect of navafenterol against two non-muscarinic contractile agonists, histamine and thromboxane A2 (TxA2) analog (U46619). Navafenterol pre-treatment significantly attenuated histamine-induced bronchoconstriction and β2AR antagonist propranolol reversed this inhibitory effect. TxA2 analog-induced bronchoconstriction was attenuated by navafenterol pre-treatment, albeit to a lesser magnitude than that of histamine-induced bronchoconstriction. Propranolol completely reversed the inhibitory effect of navafenterol on TxA2 analog-induced bronchoconstriction. In the presence of histamine or TxA2 analog, navafenterol exhibits bronchoprotective effect in human airways and it is primarily mediated by β2AR agonism of navafenterol. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:20734409
DOI:10.3390/cells12020240