超快亲和萃取法在止咳平喘药和β2-AR之间相互作用动力学研究  

Kinetic Study on the Interaction Between AntiasthmaticDrugs and β_(2)-AR by Ultrafast Affinity Extraction

作　　者：尚丛珊[1] 侯亚妮[1] 孟婷婷[1] SHANG Cong-shan;HOU Ya-ni;MENG Ting-ting(School of Medicine,Xi'an Peihua University,Xi'an Shaanxi 710025,China)

机构地区：[1]西安培华学院医学院,陕西西安710025

出　　处：《当代化工》2022年第2期336-341,共6页Contemporary Chemical Industry

基　　金：陕西省教育厅专项项目,超快亲和萃取法在药物与β_2-肾上腺素受体相互作用中的应用研究(项目编号:19JK0636)。

摘　　要：止咳平喘药与β_(2)-肾上腺素受体(β_(2)-AR)的相互作用可对药代动力学产生显著影响。采用超快亲和萃取法,考察了硫酸沙丁胺醇、硫酸特布他林、甲氧那明、盐酸异丙肾上腺素和盐酸麻黄碱5种工具药与β_(2)-AR微柱的反应。在亲和力10^(4)~10^(5)mol范围内、pH为7.4和37℃条件下测定了这些药物与β_(2)-AR的结合平衡常数,与文献值符合较好。使用单一位点结合模型时平衡常数与受体及药物浓度呈依赖性关系。用超快亲和萃取法测到的表观离解速率常数在1.1~23 s^(-1)之间,并与药物和受体浓度有关。随着药物与受体比例的降低,表观解离速率也降低。此外,本研究中采用的超快亲和萃取法也可用于分析生物医学领域其他溶质-受体相互作用。Interactions withβ_(2)-Adrenoreceptor(β_(2)-AR)can have significant effect on the behavior and pharmacokinetics of drugs.Ultrafast affinity extraction was used withβ_(2)-AR microcolumns to examine these processes for several model drugs(including salbutamol sulfate,terbutaline sulfate,methoxynamine,isoprenaline hydrochloride,ephedrine hydrochloride).The association equilibrium constants measured for these drugs with solubleβ_(2)-AR by ultrafast affinity extraction were in the general range of 10^(4)~10^(5)mol molat pH 7.4 and 37℃,and gave good agreement with literature values.Some of these values were dependent on the relative drug and protein concentrations that were present when using a single-site binding model,these results suggested a more complex mixed-mode interaction was actually present,which was also then used to analyze the data.The apparent dissociation rate constants that were obtained by ultrafast affinity extraction when using a single-site model varied from 0.14 s^(-1)to 7.0 s^(-1) and were dependent on the relative drug and protein concentrations.Lower apparent dissociation rate constants were obtained by this approach as the relative amount of drug versus protein was decreased.This information should be useful in better understanding how these and other drugs interact withβ_(2)-AR in the circulation.In addition,the chromatographic approaches that were optimized and used in this report to examine these systems can be adapted for the analysis of other solute-protein interactions of biomedical interest.

关 键 词：肾上腺素受体 β_(2)-AR 平衡常数 超快亲和萃取法 

分 类 号：TQ461[化学工程—制药化工]