title: Erythromycin inhibits ATP-induced intracellular calcium responses in bovine tracheal epithelial cells.
abstract: Erythromycin (EM) therapy is known to decrease airway secretion in chronic inflammatory airway diseases such as diffuse panbronchiolitis. Airway secretion is regulated by intracellular Ca2+ concentration ([Ca2+]i). To elucidate the intracellular site of action of EM in airway epithelium, we examined the effect of EM on Ca2+ dynamics in cultured bovine tracheal epithelial cells using fura-2. EM per se did not cause any change in [Ca2+]i. Adenosine triphosphate (ATP; 10(-4) M) induced a biphasic [Ca2+]i increase, consisting of a transient response followed by a sustained response. Pretreatment of cells with EM had little effect on the ATP-induced transient Ca2+ response but substantially reduced the sustained response in a dose-dependent manner. Clarithromycin, another 14-membered ring macrolide, likewise showed the inhibitory effect, but ampicillin and cephasolin did not. Uridine triphosphate (UTP; 10(-4) M) induced a biphasic [Ca2+]i increase similar to ATP, and the UTP-induced sustained Ca2+ response was also inhibited by EM. In Ca2+-deficient medium (1 mM ethyleneglycol-bis-(beta-aminoethyl ether)-N, N'-tetraacetic acid [EGTA]) or in the presence of La3+, the sustained Ca2+ response disappeared, suggesting that EM may inhibit Ca2+ influx induced by P2u purinoceptor stimulation. In single-cell Ca2+ image analysis, low concentration of ATP (10(-6) M) induced Ca2+ oscillations, which were also inhibited by EM. The disappearance of [Ca2+]i oscillations after addition of EM was similar to that after addition of EGTA. These results suggest that EM may decrease Ca2+-dependent airway secretion by inhibiting agonist-stimulated Ca2+ influx.
authors.affiliation: First Department of Medicine and Second Department of Physiology, Tokyo Women's Medical College, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kondo
authors.forename: S
authors.initials: S
authors.lastname: Kanoh
authors.forename: J
authors.initials: J
authors.lastname: Tamaoki
authors.forename: H
authors.initials: H
authors.lastname: Shirakawa
authors.forename: S
authors.initials: S
authors.lastname: Miyazaki
authors.forename: A
authors.initials: A
authors.lastname: Nagai
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D004917:Erythromycin / Q000494:pharmacology*; D005453:Fluorescence; D016257:Fura-2 / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007811:Lanthanum / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*; D014544:Uridine Triphosphate / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004917:Erythromycin; D007811:Lanthanum; D000255:Adenosine Triphosphate; D014700:Verapamil; D002118:Calcium; D016257:Fura-2; D014544:Uridine Triphosphate