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Erythromycin relaxes BALB/c mouse airway smooth muscle

Cai, Yan, Lei, Ying, Chen, Jingguo, Cao, Lei, Yang, Xudong, Zhang, Kanghuai, Cao, Yongxiao
Life sciences 2019 v.221 pp. 135-142
agonists, asthma, atropine, bitterness, calcium, carbachol, cyclic AMP, enzyme immunoassays, epithelium, erythromycin, indomethacin, isoprenaline, ligands, mice, myocytes, ouabain, potassium channels, potassium chloride, serotonin, smooth muscle, taste receptors
Bitter taste receptor (TAS2R) agonists have bronchodilatory potentials. Erythromycin is a ligand of TAS2R10, but its relaxant profile is unknown. This study was performed to understand the relaxant effects of erythromycin and its potential mechanism.Airway resistance was tested by the whole body plethysmography in the ovalbumin-aluminum hydroxide induced asthma model mice. Tracheal ring segment myography was used to investigate the isometric tension of the smooth muscle. The cyclic adenosine monophosphate (cAMP) concentration was measured by enzyme immunoassay kit. Changes in the calcium influx in airway smooth muscle cells (ASMCs) were surveyed using a real-time confocal microscopy.Erythromycin significantly relieved airway hyperreactivity in asthma model mice. Erythromycin relaxed mouse tracheal segments precontracted with carbachol, KCl, 5-hydroxytryptamine and U46619, and further dilated the tracheal rings relaxed by isoprenaline or atropine. Epithelium removal, indomethacin or NS-398 partially reduced the relaxation. U73122, 2-APB, iberiotoxin or ouabain did not change the concentration-relaxation curves of erythromycin on tracheal segments. Erythromycin didn't elevate cAMP level. CaCl2-induced contraction in the K+-rich solution was impaired by erythromycin in the Ca2+-free solution. The intercellular Ca2+ level in the ASMCs was decreased by erythromycin, which was partly inhibited by Bay K8644 but not gallein.Erythromycin had marked bronchodilatory effect. The relaxation might be related to the L-type voltage-dependent calcium channel, but not the gustducin-associated βγ/phospholipase-Cβ/inositol 1,4,5-tri-phosphate receptor/large conductance Ca2+-activated K+ channel pathway or a cAMP-dependent way.