Trimethoprim and tetracycline inhibit airway epithelial sodium absorption

Am J Respir Crit Care Med. 1996 Jul;154(1):18-23. doi: 10.1164/ajrccm.154.1.8680677.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Adult
  • Amiloride / pharmacology
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents / pharmacology*
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis / physiopathology
  • Diuretics / pharmacology
  • Epithelium / metabolism
  • Female
  • Humans
  • In Vitro Techniques
  • Ion Transport / drug effects
  • Male
  • Membrane Potentials / drug effects
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / physiopathology
  • Sheep
  • Sodium / metabolism*
  • Tetracycline / pharmacology*
  • Trachea / metabolism*
  • Trimethoprim / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Diuretics
  • Amiloride
  • Sodium
  • Trimethoprim
  • Tetracycline