Effect of Clarithromycin on Transepithelial Potential Difference in Rabbit Tracheal Mucosa

Abstract

Erythromycin's effectiveness in treating chronic airway diseases such as panbroncholitis may derive from its ability to inhibit chloride ion (Cl−) transport across airway mucosa, and hence to alleviate the excess sputum secretion characteristic of these disorders. To determine whether the newly developed macrolide antibiotic clarithromycin (CAM) has a similar effect, we studied its influence on the Cl− diffusion potential difference (Cl-PD) across rabbit tracheal mucosa using a high-impedance voltmeter under open-circuit conditions in vivo. Superfusion of the tracheal mucosal surface with 10−5 or 10−4 M CAM in the presence of the sodium-channel blocker amiloride had no effect on the CI-PD. Intravenous administration of CAM at 10 mg/kg, however, caused a rapid decrease in Cl-PD from 10.8 ± 0.7 to 6.9 ± 0.4 mV (P < 0.001). This effect was dose-dependent: The maximum decrease from baseline CI-PD was 5.6 ± 0.9 mV (P < 0.001), and the dose of CAM required to produce a half-maximal effect (EC50) was 2.7 mg/kg. Intravenous erythromycin decreased CI-PD to the same extent, whereas aminobenzyl penicillin, cefazolin and amikacin had no effect. These results suggest that CAM may inhibit Cl− secretion by airway epithelial cells in vivo, consequently decreasing water movement from the submucosa to the mucosa and perhaps inhibiting airway secretion. Erythromycin's effectiveness in treating chronic airway diseases such as panbroncholitis may derive from its ability to inhibit chloride ion (Cl−) transport across airway mucosa, and hence to alleviate the excess sputum secretion characteristic of these disorders. To determine whether the newly developed macrolide antibiotic clarithromycin (CAM) has a similar effect, we studied its influence on the Cl− diffusion potential difference (Cl-PD) across rabbit tracheal mucosa using a high-impedance voltmeter under open-circuit conditions in vivo. Superfusion of the tracheal mucosal surface with 10−5 or 10−4 M CAM in the presence of the sodium-channel blocker amiloride had no effect on the CI-PD. Intravenous administration of CAM at 10 mg/kg, however, caused a rapid decrease in Cl-PD from 10.8 ± 0.7 to 6.9 ± 0.4 mV (P < 0.001). This effect was dose-dependent: The maximum decrease from baseline CI-PD was 5.6 ± 0.9 mV (P < 0.001), and the dose of CAM required to produce a half-maximal effect (EC50) was 2.7 mg/kg. Intravenous erythromycin decreased CI-PD to the same extent, whereas aminobenzyl penicillin, cefazolin and amikacin had no effect. These results suggest that CAM may inhibit Cl− secretion by airway epithelial cells in vivo, consequently decreasing water movement from the submucosa to the mucosa and perhaps inhibiting airway secretion.