[Effect of roxithromycin on ciliary motility of rabbit tracheal epithelium in culture].
Mucociliary transport plays an important role in the lung defense mechanism by clearing inhaled particles and bacteria from the respiratory tract. In the present study, we tried to determine whether roxithromycin (RXM), a new semisynthetic macrolide, can affect airway mucociliary functions and, if so, what the mechanism of its action is. To do so we measured ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method. Addition of RXM (10(-4) M) to a Rose chamber containing epithelial cells caused a rapid increase in CBF from 12.1 +/- 0.6 to 16.2 +/- 0.8 Hz (mean +/- SE, p less than 0.001) within 5 min. This effect was dose-dependent, the maximal increase from the baseline CBF and EC50 being 34.6 +/- 5.0% and 3 x 10(-6)M, respectively. The increase in CBF produced by RXM (3 x 10(-6)M) was not influenced by pretreatment of cells with the beta-adrenergic blocker propranolol, the lipoxygenase inhibitor AA-861, or the Ca(2+)-channel blocker verapamil, but it was partially reduced by the cyclooxygenase inhibitor indomethacin (p less than 0.05). Intracellular cyclic AMP levels were increased by 10(-4)M RXM from 42.3 +/- 8.7 to 72.7 +/- 7.0 pmoles/mg protein (p less than 0.05). These results indicate that RXM stimulates ciliary motility; an effect that may be attributed at least in part to the synthesis of cyclooxygenase products and cyclic AMP, and suggest that this macrolide could be useful in treating patients with impaired mucociliary transport in the airway.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College.
Takeyama
K
K
Chiyotani
A
A
Sakai
N
N
Yamauchi
F
F
Takizawa
T
T
D000818:Animals; D002923:Cilia / Q000187:drug effects; D000242:Cyclic AMP / Q000032:analysis; D066298:In Vitro Techniques; D009092:Mucous Membrane / Q000187:drug effects; D011817:Rabbits; D015575:Roxithromycin / Q000494:pharmacology*; D014132:Trachea / Q000737:chemistry / Q000187:drug effects*
D015575:Roxithromycin; D000242:Cyclic AMP