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Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non-cystic fibrosis epithelia.
2010 (Engelska)Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 118, nr 12, s. 982-990Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
2010. Vol. 118, nr 12, s. 982-990
Nationell ämneskategori
Klinisk medicin
Identifikatorer
URN: urn:nbn:se:liu:diva-113913DOI: 10.1111/j.1600-0463.2010.02680.xPubMedID: 21091780OAI: oai:DiVA.org:liu-113913DiVA, id: diva2:785601
Tillgänglig från: 2015-02-03 Skapad: 2015-02-03 Senast uppdaterad: 2017-12-05

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