Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non-cystic fibrosis epithelia.

Abstract

The lantibiotic duramycin (Moli1901, Lancovutide) has been suggested as a drug of choice in the treatment for cystic fibrosis (CF). It has been proposed that duramycin may stimulate chloride secretion through Ca²(+) -activated Cl⁻ channels (CaCC). We investigated whether duramycin exhibited any effect on Cl⁻ efflux and intracellular Ca²(+) concentration ([Ca²(+)](i)) in CF and non-CF epithelial cells. Duramycin did stimulate Cl⁻ efflux from CF bronchial epithelial cells (CFBE) in a narrow concentration range (around 1 μM). However, 100 and 250 μM of duramycin inhibited Cl⁻ efflux from CFBE cells. An inhibitor of the CF transmembrane conductance regulator (CFTR(inh)₋₁₇₂) and a blocker of the capacitative Ca²(+) entry, gadolinium chloride, inhibited the duramycin-induced Cl⁻ efflux. No effect on Cl⁻ efflux was observed in non-CF human bronchial epithelial cells (16HBE), human airway submucosal gland cell line, human pancreatic epithelial cells, CF airway submucosal gland epithelial cells, and CF pancreatic cells. The [Ca²(+)](i) was increased by 3 μM duramycin in 16HBE cells, but decreased after 1, and 3 μM of duramycin in CFBE cells. The results suggest that the mechanism responsible for the stimulation of Cl⁻ efflux by duramycin is mainly related to unspecific changes of the cell membrane or its components rather than to effects on CaCC.

• Authors: Igor Oliynyk, Georgia Varelogianni, Godfried M Roomans, Marie Johannesson
• Journal: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica (APMIS) Vol. 118 Issue 12 Pg. 982-90 (Dec 2010) ISSN: 1600-0463 [Electronic] Denmark
• PMID: 21091780 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. Journal Compilation © 2010 APMIS.

Chemical References

• Bacteriocins
• Chlorides
• Peptides
• Cystic Fibrosis Transmembrane Conductance Regulator
• duramycin
• Calcium

Topics

• Bacteriocins (pharmacology)
• Calcium (metabolism)
• Cell Line
• Chlorides (metabolism)
• Cystic Fibrosis (drug therapy, metabolism)
• Cystic Fibrosis Transmembrane Conductance Regulator (metabolism)
• Epithelial Cells
• Humans
• Ion Transport (physiology)
• Microscopy, Confocal
• Microscopy, Fluorescence
• Peptides (pharmacology)