title: 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.affiliation: Örebro University, Örebro University Hospital, Sweden. igor.oliynyk@oru.se
authors.forename: Igor
authors.initials: I
authors.lastname: Oliynyk
authors.forename: Georgia
authors.initials: G
authors.lastname: Varelogianni
authors.forename: Godfried M
authors.initials: GM
authors.lastname: Roomans
authors.forename: Marie
authors.initials: M
authors.lastname: Johannesson
mesh_terms: D001430:Bacteriocins / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002712:Chlorides / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004847:Epithelial Cells; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000494:pharmacology*
chemical_list: D001430:Bacteriocins; D002712:Chlorides; D010455:Peptides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C040522:duramycin; D002118:Calcium