用细胞膜色谱法研究药物和毒蕈碱受体的亲和作用(英文)

目的　观察细胞膜色谱法是否可以反映药物和毒蕈碱受体结合的特异性和选择性。方法　将大鼠心房肌细胞膜固定于硅胶载体表面制备成富含毒蕈碱受体的心房肌细胞膜固定相 ,用细胞膜色谱法研究不同药物和细胞膜固定相上毒蕈碱受体的亲和力。结果　不同药物在细胞膜固定相上的保留因子顺序为 :左旋羟苯乙酸奎宁酯 >哌仑西平 >阿托品>4 DAMP >AF DX116>毛果芸香碱 >氯化乙酰胆碱。保留因子与亲和力之间存在一定的正相关关系(r =0 .9,P <0 .0 5 ) ,但是有些药物的保留因子异常。结论　细胞膜色谱法可以作为初步观察药物和受体的亲和作用的方法 ,但其准确性需用传统的放射配体结合实验方法验证

Evaluation of drug-muscarinic receptor affinities by using cell membrane chromatography

AIM To evaluate if cell membrane chromatography(CMC) can be used to reflect the selectivity and specificity of drug-muscarinic acetylcholine receptor (mAChR) interaction. METHODS The cell membrane stationary phase (CMSP) was prepared by immobilizing rat atrium cell membrane on the surface of a silica carrier and used for the rapid on-line chromatographic evaluation of ligand binding affinities to mAChR. RESULTS The capacity factor profiles in rat atrium CMSP were: (-)QNB(11.5)>pirenzepine(4.8)>atropine(4.2)>4-DAMP (3.5)>AF-DX116(2.4)>pilocarpine(1.14)>acetylcholine(1.02). Those results compared with the affinity rank orders obtained from radioligand binding assays using the same atrium tissue indicated there was a positive correlation (r= 0.9, P<0.05) between the both data sets. However, there were some unusual capactity factors. CONCLUSION CMC method can be used to preliminarily evaluate drug-receptor affinities for drug candidates but the accuracy should be validated by traditional radioligand binding assay.