title: Trimethoprim and tetracycline inhibit airway epithelial sodium absorption.
abstract: 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.
authors.affiliation: Ion Transport Unit, National Heart and Lung Institute, London, United Kingdom.
authors.forename: P G
authors.initials: PG
authors.lastname: Middleton
authors.forename: D M
authors.initials: DM
authors.lastname: Geddes
authors.forename: E W
authors.initials: EW
authors.lastname: Alton
mesh_terms: 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*
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D004232:Diuretics; D000584:Amiloride; D012964:Sodium; D014295:Trimethoprim; D013752:Tetracycline