Correspondence

Gentamicin and CFTR

N Engl J Med 2003; 349:2570December 25, 2003

Article

To the Editor:

Wilschanski et al. (Oct. 9 issue)1 report that full-length cystic fibrosis transmembrane conductance regulator (CFTR) protein was expressed more effectively on the surface of nasal epithelial cells after gentamicin treatment than after placebo in patients with cystic fibrosis who had premature stop codons. Bedwell et al. observed that the expression of CFTR at the apical plasma membrane was restored after administration of the aminoglycoside antibiotic G-418 and that further mobilization of CFTR at this location was promoted by cyclic AMP (cAMP) stimulation.2 CFTR is normally recycled between the apical plasma membrane and an early endosomal compartment.3 The cAMP-dependent activation of CFTR inhibits the endocytosis of CFTR from the apical membrane and stimulates the movement of CFTR from the early endosomes to the apical plasma membrane.4 Therefore, the addition of cAMP to gentamicin could be more effective than the use of gentamicin alone in correcting the electrophysiological abnormalities caused by CFTR dysfunction.

Yujiro Kida, M.D., Ph.D.
Tokyo Metropolitan Komagome Hospital, Tokyo 113-8677, Japan

4 References

1. 1

   Wilschanski M, Yahav Y, Yaacov Y, et al. Gentamicin-induced correction of CFTR function in patients with cystic fibrosis and CFTR stop mutations. N Engl J Med 2003;349:1433-1441
   Full Text | Web of Science | Medline

2. 2

   Bedwell DM, Kaenjak A, Benos DJ, et al. Suppression of CFTR premature stop mutation in a bronchial epithelial cell line. Nat Med 1997;3:1280-1284
   CrossRef | Web of Science | Medline

3. 3

   Bradbury NA, Jilling T, Berta G, Sorscher EJ, Bridges RJ, Kirk KL. Regulation of plasma membrane recycling by CFTR. Science 1992;256:530-532
   CrossRef | Web of Science | Medline

4. 4

   Prince LS, Workman RB Jr, Marchase RB. Rapid endocytosis of the cystic fibrosis transmembrane conductance regulator chloride channel. Proc Natl Acad Sci U S A 1994;91:5192-5196
   CrossRef | Web of Science | Medline

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