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Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non‐cystic fibrosis epithelia
Author(s) -
OLIYNYK IGOR,
VARELOGIANNI GEORGIA,
ROOMANS GODFRIED M.,
JOHANNESSON MARIE
Publication year - 2010
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1600-0463.2010.02680.x
Subject(s) - cystic fibrosis , efflux , cystic fibrosis transmembrane conductance regulator , chloride channel , secretion , intracellular , biology , chemistry , microbiology and biotechnology , biochemistry , genetics
Oliynyk I, Varelogianni G, Roomans GM, Johannesson M. Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non‐cystic fibrosis epithelia. APMIS 2010; 118: 982–90. 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 Ca 2+ ‐activated Cl − channels (CaCC). We investigated whether duramycin exhibited any effect on Cl − efflux and intracellular Ca 2+ concentration ([Ca 2+ ] 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 Ca 2+ 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 [Ca 2+ ] 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.