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

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Abstract:

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 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 (CFTRinh-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.

Keywords: Duramycin; airway epithelium; chloride efflux; cystic fibrosis; intracellular calcium

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1600-0463.2010.02680.x

Affiliations: School of Health and Medical Sciences, Örebro University, Örebro University Hospital, Örebro, Sweden

Publication date: December 1, 2010

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