In:
Clinical and Experimental Pharmacology and Physiology, Wiley, Vol. 46, No. 4 ( 2019-04), p. 329-336
Abstract:
Azithromycin ( AZM ) has been used for the treatment of asthma and chronic obstructive pulmonary disease ( COPD ); however, the effects and underlying mechanisms of AZM remain largely unknown. The effects of AZM on airway smooth muscles ( ASM s) and the underlying mechanisms were studied using isometric muscle force measurements, the examination of lung slices, imaging, and patch‐clamp techniques. AZM completely inhibited acetylcholine ( ACH )‐induced precontraction of ASM s in animals (mice, guinea pigs, and rabbits) and humans. Two other macrolide antibiotics, roxithromycin and Klaricid, displayed a decreased inhibitory activity, and the aminoglycoside antibiotics penicillin and streptomycin did not have an inhibitory effect. Precontractions were partially inhibited by nifedipine (selective inhibitor of L‐type voltage‐dependent Ca 2+ channels ( LVDCC s)), Pyr3 (selective inhibitor of TRPC 3 and/or STIM /Orai channels, which are nonselective cation channels ( NSCC s)), and Y‐27632 (selective inhibitor of Rho‐associated kinase ( ROCK )). Moreover, LVDCC ‐ and NSCC ‐mediated currents were inhibited by AZM , and the latter were suppressed by the muscarinic (M) 2 receptor inhibitor methoctramine. AZM inhibited LVDCC Ca 2+ permeant ion channels, M2 receptors, and TRPC 3 and/or STIM /Orai, which decreased cytosolic Ca 2+ concentrations and led to muscle relaxation. This relaxation was also enhanced by the inhibition of Ca 2+ sensitization. Therefore, AZM has potential as a novel and potent bronchodilator. The findings of this study improve the understanding of the effects of AZM on asthma and COPD .
Type of Medium:
Online Resource
ISSN:
0305-1870
,
1440-1681
DOI:
10.1111/cep.2019.46.issue-4
DOI:
10.1111/1440-1681.13062
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2020033-X
SSG:
15,3
Permalink