哮喘联盟

   摘要
   目的：据报道，非甾体类抗炎药（NSAIDs）能调节有机阳离子转运体（OCT）。本试验旨在研究NSAIDs存在的情况下，硫酸沙丁胺醇（哮喘发作治疗时常用的β2受体激动剂）通过单层Calu-3呼吸道上皮细胞的动力学。
   方法：通过液体覆盖培养（LCC）法，在0.33 cm2 Transwell聚酯纤维细胞培养板上培养单层Calu-3细胞。培养11天至14天，评价上皮细胞的阻力、紧密连接完整性和OCT表达（western blot分析）。研究不同浓度沙丁胺醇通过单层细胞的能力。通过评价顶-基底（a-b）和基底-顶（b-a）的转运来研究沙丁胺醇的定向转运。研究非特异性OCT抑制剂（四乙基铵，TEA）和三个NSAIDs（阿司匹林、布洛芬和吲哚美辛）对沙丁胺醇摄取的影响。
   结果：硫酸沙丁胺醇的转运随着浓度的增加而增加，随后达到平台水平，表明存在转运体介导的摄取。Western blot分析显示存在OCT1-3、N1和N2亚型，表明存在功能性转运体。0.1 mM沙丁胺醇通过单层上皮的表观通透（Papp）表现为a-b的定向转运，而TEA能抑制约70%的转运，表明OCT介导了摄取。与此类似，当存在所有三个NSAIDs时，0.1 mM沙丁胺醇的摄取下降，表明NSAIDs通过作用于OCT转运体抑制沙丁胺醇通过支气管上皮细胞。
   结论：本研究显示，NSAIDs能影响沙丁胺醇通过体外Calu-3细胞系统的动力学。
 

（苏楠 审校）
J Asthma. 2013 Feb 13. [Epub ahead of print]

 

Salbutamol sulphate absorption across Calu-3 bronchial epithelia cell monolayer is inhibited in the presence of common anionic NSAIDs.
 
Mamlouk M, Young PM, Bebawy M, Haghi M, Mamlouk S, Mulay V, Traini D.

Source
Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney , NSW 2006 , Australia.

Abstract 
PURPOSE: The aim of this study was to characterize the permeability kinetics of salbutamol sulphate, a commonly used β2-agonist in the treatment of asthma exacerbation, across Calu-3 respiratory epithelial cell monolayers in the presence of non-steroidal anti-inflammatory drugs (NSAIDs), as they have been implicated to be able to modulate organic cation transporters (OCT).
METHODS: Calu-3 cell monolayers were grown in a liquid covered culture (LCC) configuration on 0.33 cm(2) Transwell polyester cell culture supports. Monolayers, cultured between 11 and 14 days were evaluated for epithelial resistance, tight junction integrity and expression of OCT using Western blot analysis. The transport of salbutamol across the monolayer was studied as a function of concentration. Directional transport was investigated by assessing apical-basal (a-b) and basal- apical (b-a) directions. The influence of a non-specific OCT inhibitor (tetraethylammonium, TEA) and three NSAIDs (aspirin, ibuprofen and indomethacin) on the uptake of salbutamol was studied.
RESULTS: The flux of salbutamol sulphate increased with increasing concentration, before reaching a plateau suggesting the involvement of a transport mediated uptake mechanism. Western blot analysis detected the presence of OCT1-3 and N1 and N2 sub-types suggesting the presence of functioning transporters. The apparent permeability (P(app)) of 0.1 mM salbutamol across the epithelial monolayer displayed directional transport in the a-b direction which was inhibited by ˜70% in the presence of TEA, suggesting OCT mediated uptake. Likewise, the uptake of 0.1 mM salbutamol was decreased in the presence of all three NSAIDs supporting a mechanism whereby NSAIDs inhibit absorption of salbutamol across the bronchial epithelium via effects on the OCT transporters.
CONCLUSION: This study demonstrates that NSAIDS influence the uptake kinetics of salbutamol in an in vitro Calu-3 cell system.

J Asthma. 2013 Feb 13. [Epub ahead of print]