Örebro University, Örebro University Hospital, Sweden.
APMIS. 2010 Dec;118(12):982-90. doi: 10.1111/j.1600-0463.2010.02680.x. Epub 2010 Sep 14.
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(+)) 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(+) 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.
杆菌肽（Moli1901，Lancovutide）作为囊性纤维化（CF）治疗的首选药物已被提出。有人提出杆菌肽可能通过 Ca²（+）激活的 Cl⁻通道（CaCC）刺激 Cl⁻分泌。我们研究了杆菌肽是否对 CF 和非 CF 上皮细胞中的 Cl⁻外排和细胞内 Ca²（+）浓度（[Ca²（+）]（i））有任何影响。杆菌肽确实在狭窄的浓度范围内（约 1 μM）刺激 CF 支气管上皮细胞（CFBE）中的 Cl⁻外排。然而，100 和 250 μM 的杆菌肽抑制 CFBE 细胞的 Cl⁻外排。CF 跨膜电导调节剂（CFTR(inh)₋₁₇₂）的抑制剂和电容性 Ca²（+）进入的阻断剂，氯化钆，抑制了杆菌肽诱导的 Cl⁻外排。非 CF 人支气管上皮细胞（16HBE）、人气道粘膜下腺细胞系、人胰腺上皮细胞、CF 气道粘膜下腺上皮细胞和 CF 胰腺细胞中未观察到 Cl⁻外排的影响。3 μM 杆菌肽增加了 16HBE 细胞中的 [Ca²（+）]（i），但在 CFBE 细胞中，1 和 3 μM 的杆菌肽后减少了。结果表明，杆菌肽刺激 Cl⁻外排的机制主要与细胞膜或其成分的非特异性变化有关，而不是与 CaCC 有关。
