Trimethoprim and tetracycline inhibit airway epithelial sodium absorption.
Despite their frequent use in the treatment of chronic lung disease, the effect of antibiotics on the airway mucosa has not been defined. We have assessed the effect of a number of antibiotics on the ion transport processes of airway epithelia. Initial evaluation performed on sheep tracheal epithelium in vitro demonstrated that trimethoprim and tetracycline induced a rapid decrease in electrogenic ion transport. These responses were fully reversible, mediated through the mucosal surface, and reduced by amiloride pretreatment, suggesting inhibition of Na+ absorption. Serosal application of erythromycin produced a gradual decrease in short-circuit current, whereas other antibiotics (ampicillin, ceftazidime, colistin, chloramphenicol, gentamicin, and sulfamethoxazole) caused no significant change within 30 min of addition. In healthy human volunteers, trimethoprim and tetracycline induced a rapid decrease in nasal potential difference, which was attenuated by amiloride pretreatment. In subjects with cystic fibrosis, who exhibit increased Na+ absorption across respiratory epithelia, the responses to trimethoprim and tetracycline were enhanced, providing further evidence that these drugs inhibit Na+ absorption. In conclusion, this study has identified two antibacterial agents that also reduce the Na+ absorption found in CF. These drugs may offer combined effects for the treatment of CF.
Middleton
P G
PG
Ion Transport Unit, National Heart and Lung Institute, London, United Kingdom.
Geddes
D M
DM
Alton
E W
EW
D000042:Absorption; D000328:Adult; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000378:metabolism / Q000503:physiopathology; D004232:Diuretics / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009297:Nasal Mucosa / Q000378:metabolism / Q000503:physiopathology; D012756:Sheep; D012964:Sodium / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology*; D014132:Trachea / Q000378:metabolism*; D014295:Trimethoprim / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004232:Diuretics; D000584:Amiloride; D012964:Sodium; D014295:Trimethoprim; D013752:Tetracycline