Azithromycin has a direct relaxant effect on precontracted airway smooth muscle.
Macrolides have been proven to have beneficial bacteriostatic and anti-inflammatory properties, but very little is known about the potential value of their bronchodilatory effect. Therefore, in the present study we investigated the effect of azithromycin on contractile responses of isolated rabbit tracheal strips to carbachol or KCl. Azithromycin has a relaxant, concentration-dependent effect on tracheal strips precontracted with carbachol (300 nM), significant from the concentration of 1 muM. The mechanical removal of epithelium did not alter the effect of azithromycin. Azithromycin (100 microM) also relaxed tracheal strips precontracted with KCl (80 mM) even in the presence of atropine (100 microM). Moreover, azithromycin (100 microM) decreased contractions induced by 300 nM and 10 microM carbachol to 55.4% and 80.5% of initial contraction, respectively. The relaxant effect of azithromycin persisted in both calcium free solution and in the presence of the calcium channel antagonist, verapamil. The relaxant effect of azithromycin was not altered by the pre-treatment of preparations with the inhibitors of Ca(2+)-ATPase (cyclopiazonic acid), Na(+)-K(+) ATPase (ouabain), Rho-associated kinase [(R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride] (Y-27632) or the non-specific cAMP and cGMP phosphodiesterases inhibitor 3-isobutyl-1-methyl-2,6(1H,3H)-purinedione (IBMX). These results suggest that azithromycin has a concentration-dependent, epithelium-independent, direct relaxant effect on precontracted tracheal strips that is not mediated via inhibition of Ca(2+) influx or Ca(2+) release from intracellular stores. Also, it is not due to alteration of the function of Na(+)-K(+) ATPase and does not depend on the formation of cAMP/cGMP or the Rho/Rho-activated kinase pathway.
Daenas
Christos
C
Department of Physiology, Medical School, University of Thessaly, Larissa, Greece.
Hatziefthimiou
Apostolia A
AA
Gourgoulianis
Konstantinos I
KI
Molyvdas
Paschalis Adam
PA
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D017963:Azithromycin / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010042:Ouabain / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011817:Rabbits; D014132:Trachea / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology; D054460:rho-Associated Kinases
D000900:Anti-Bacterial Agents; D001993:Bronchodilator Agents; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D018721:Muscarinic Agonists; D010726:Phosphodiesterase Inhibitors; D010042:Ouabain; D011189:Potassium Chloride; D001285:Atropine; D017963:Azithromycin; D002217:Carbachol; D014700:Verapamil; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D000252:Calcium-Transporting ATPases; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine