Epithelial barrier modulation by a channel forming peptide.
Epithelial barrier modulation by a channel forming peptide.
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通道形成肽对上皮屏障的调节。
DOI：
10.1007/s00232-008-9099-3
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Schultz,BruceD
中科院分区：
文献类型：
--
作者：
Somasekharan,Suma;Brandt,Robert;Iwamoto,Takeo;Tomich,JohnM;Schultz,BruceD
NC-1059 is a synthetic channel-forming peptide that provides for ion transport across, and transiently reduces the barrier integrity of, cultured epithelial monolayers derived from canine kidney (MDCK cells). Experiments were conducted to determine whether epithelial cells derived from other sources were similarly affected. Epithelial cells derived from human intestine (T-84), airway (Calu-3), porcine intestine (IPEC-J2) and reproductive duct (PVD9902) were grown on permeable supports. Basal short circuit current (Isc) was <3 μA cm−2for T-84, IPEC-J2 and PVD9902 cell monolayers and <8 μA cm−2for Calu-3 cells. Apical NC-1059 exposure caused, in all cell types, an increase inIscto >15 μA cm−2, indicative of net anion secretion or cation absorption, which was followed by an increase in transepithelial conductance (in mS cm−2: T-84, 1.6 to 62; PVD9902, 0.2 to 51; IPEC-J2, 0.3 to 26; Calu-3, 2.3 to 13). These results are consistent with the peptide affecting transcellular ion movement, with a likely effect also on the paracellular route. NC-1059 exposure increased dextran permeation when compared to basal permeation, which documents an effect on the paracellular pathway. In order to evaluate membrane ion channels, experiments were conducted to study the dose dependence and stability of the NC-1059-induced membrane conductance inXenopuslaevisoocytes. NC-1059 induced a dose-dependent increase in oocyte membrane conductance that remained stable for greater than 2 h. The results demonstrate that NC-1059 increases transcellular conductance and paracellular permeation in a wide range of epithelia. These effects might be exploited to promote drug delivery across barrier epithelia.
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