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

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 mu M). However, 100 and 250 mu M 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 mu M duramycin in 16HBE cells, but decreased after 1, and 3 mu M 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.