摘要
目的探讨苯环喹溴铵对毒蕈碱样乙酰胆碱受体(M受体)亚型的选择性。方法以表达单一M受体亚型的CHO细胞株进行细胞与[3H]-QNB的饱和实验,并进行竞争抑制药和[3H]-QNB与M受体亚型的竞争结合实验,计算Kd值和Ki值。通过离体膀胱肌条实验评价苯环喹溴铵干预乙酰胆碱对离体膀胱肌条的收缩作用,计算pA2值。观察苯环喹溴铵对麻醉犬心率、心电图的影响及其对小鼠气管分泌功能的影响。结果苯环喹溴铵对3种细胞的抑制强度为CHOM3>CHOM1>CHOM2,对CHOM3和CHOM1的抑制能力相似,明显高于对CHOM2的抑制能力(P<0.01)。苯环喹溴铵可拮抗乙酰胆碱对离体膀胱肌条的收缩作用,使量效曲线平行右移,PA2值为7.09±s0.06。与溶媒组相比,苯环喹溴铵经鼻给药后对麻醉犬的心率和心电图无明显影响(P>0.05)。苯环喹溴铵大剂量组给药后1h、2h和中剂量组给药后2h能明显减少小鼠气管分泌物的分泌(P<0.01)。结论苯环喹溴铵是一种可选择性作用于M1和M3受体亚型的拮抗药。
AIM To investigate the selectivity of bencycloquidium bromide （BCQB） to the subtypes of muscarinic receptors.METHODS CHO cells expressed single subtype of muscarinic receptor were used for the radioligand-binding assay.Saturation experiments between [3H]-QNB and the cells,and competition binding experiments between inhibitors and [3H]-QNB with subtypes of muscarinic receptors were performed to obtain values for both Kd and Ki.Contractions of isolated bladder strips from guinea pigs were examined in vitro to investigate the selectivity of BCQB.Effects of BCQB on the heart and tracheal gland were also observed.RESULTES The inhibitory potency of BCQB to the cell lines was as CHOM3 CHOM1 CHOM2,in which the selectivity of BCQB to M1 and M3 muscarinic receptors were close to each other and were higher than that to M2 muscarinic receptor.BCQB shifted the dose-response curve of isolated bladder strips to the right in a parallel fashion.The pA2 value of BCQB was 7.09 ± s 0.06.Compared with vehicle group,BCQB had no obvious effects on the heart rate and electrocardiogram （P 0.05） in anesthetized Beagle dogs after intranasal medication.The secretion of phenol red in the trachea of mice decreased at 1 h,2 h in BCQB high dose group,2 h in BCQB medium dose group （P 0.01）.CONCLUSION BCQB is a muscarinic receptor antagonist,which has relatively high selectivity towards M1 and M3 muscarinic receptors.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2010年第1期45-49,共5页
Chinese Journal of New Drugs and Clinical Remedies
基金
科技部2006年度科技型中小企业技术创新基金项目(06C26211100623)
关键词
受体
毒蕈碱
乙酰胆碱
CHO细胞
苯环喹溴铵
receptors
muscarinic
acetylcholine
CHO cells
bencycloquidium bromide
