摘要
目的 比较碘化二甲基粉防已碱 (DMTI)和二氢 - β -刺桐啶碱 (dHβE)对烟碱诱发电流的抑制作用 ,并确定DMTI在烟碱受体上的作用位点。方法 取新生Wistar大鼠骨骼肌细胞体外培养获得肌球 ,用膜片箝全细胞记录技术 ,观察肌球的烟碱诱发电流。结果 0 .0 8mmol·L-1DMTI抑制烟碱诱发电流幅度的作用与 0 .0 2mmol·L-1dHβE的作用类似。向单个细胞持续给烟碱覆盖诱发电流的全过程。电流的衰减过程反映了烟碱受体的失敏 ,DMTI使烟碱诱发电流的慢失敏时间常数减小 ,即加速受体失敏 ,但没发现dHβE有这种作用。在 - 30、- 5 0、- 70、- 90mV钳制电压处观察电压改变对DMTI和对dHβE作用的影响 ,没有发现DMTI或dHβE抑制烟碱电流的作用随钳制电压改变而改变 ,即两者的作用都是非电压依赖性的 ,表明DMTI和dHβE都不是离子通道阻断剂。结论 由于烟碱受体是变构蛋白 ,变构调节剂能加速受体失敏 ,DMTI的抑制作用符合变构调节剂的作用特点 ,并且作用位点不在烟碱受体离子通道 。
Aim To investigate the difference of inhibitory effect between Dimethyl Tetrandrine Iodide (DMTI) and Dihydro β erythroidine (dHβE) on muscle nicotinic receptor and locate their action sites on nicotinic receptor.Methods whole cell patch clamp technique was used to record nicotine induced current in cultured myoball from skeleton muscle of neonatal Wistar rats.Results DMTI inhibited nicotine induced current amplitude,and the effect of 0.08mmol·L -1 DMTI was similar with that of 0.02mmol·L -1 dHβE. Decay of nicotine-induced current in the course of nicotine administration reflexes desensitization of nicotinic receptor,and DMTI decreased slow time constant (ιs) of nicotine-induced current's decay.That is to say,DMTI accelerated desensitization of nicotinic receptor, which was different from dHβE. Both their inhibitory effect did not change with different holding potential from -30～-90 mV, which suggested their action sites be outside the ion channel of nicotinic receptor.Conclusion As nicotinic receptor is allosteric protein, allosteric modulation agents accelerate desensitization of nicotinic receptor.We conjectured that DMTI may be an allosteric antagonist acting outside ion channel, while dHβE could not be an allosteric modulation agent.
出处
《解放军药学学报》
CAS
2001年第3期121-124,共4页
Pharmaceutical Journal of Chinese People's Liberation Army
关键词
全细胞记录
烟碱受体
变构调节
拮抗剂
碘化二甲基粉防己碱
Whole cell recording
Nicotinic receptor
Allosteric modulation
Antagonist
Dimethyl tetrandrine iodide
