J. Tamaoki et al., EFFECTS OF MACROLIDE ANTIBIOTICS ON NEURALLY-MEDIATED CONTRACTION OF HUMAN ISOLATED BRONCHUS, Journal of allergy and clinical immunology, 95(4), 1995, pp. 853-859
Background: Long-term administration of macrolide antibiotic substance
s is an alternative therapy used in the treatment of asthma and airway
hyperresponsiveness, but neither its mechanism of action nor whether
this substance exerts an immediate action in the airways is known. Met
hods: Contractile responses of human isolated bronchial strips to elec
trical field stimulation (EFS) and acetylcholine were assessed under i
sometric conditions in the absence and presence of erythromycin, roxit
hromycin, or clarithromycin. Results: Incubation of tissues with eryth
romycin (3 X 10(-5) mol/L) attenuated the contractile responses to EFS
so that the stimulus frequency required to produce 50% of the maximal
contraction increased form 4.1 +/- 0.5 to 10.1 +/- 0.7 Hz (mean +/- S
E; p < 0.001). In contrast, contractile responses to acetylcholine wer
e not changed. Erythromycin reduced the EFS-induced contraction in a c
oncentration-dependent fashion; the maximal decrease from the baseline
response was 92.8% +/- 3.6% (p < 0.001). This inhibitory effect was n
ot altered by propranolol, indomethacin, ouabain, charybdotoxin, or me
chanical removal of the epithelium. Roxithromycin and clarithromycin l
ikewise inhibited neurally mediated contraction. Conclusions: These re
sults suggest that macrolides may inhibit cholinergic neuroeffector tr
ansmission in the human airway smooth muscle, probably by reducing exo
cytotic release of acetylcholine from the nerve terminals.