摘要
烟碱受体(nAchRs)是一种由α与β亚基所组成的同源或异源五聚体,已有研究表明心脏内含有nAChRs。为确定何种nAChRs亚基在烟碱(Nicotine)对心脏的影响中起主要调节作用,本试验利用大鼠模型进行药物试验。在给大鼠注射100μmol/L烟碱后,起初引起大鼠短暂的心率降低-7次±2%,随之出现大幅度的心率增加17次±5%,增加的心率在10 min^15 min恢复正常。烟碱引起心率的降低作用能被α7亚基特异性阻断剂α-金环蛇毒素(-αBTX,100 nmol/L)所抵消;相反,心率的增加现象在α-金环蛇毒素存在时得到延续。选择性β4亚基竞争剂金花雀碱(Cytisine)对大鼠进行注射后,结果与烟碱对大鼠心率作用的结果相似,因此在心脏交感神经末梢可能存在nAChRsβ4亚基。试验结果,显示不同的nAChRs亚基在对烟碱对心脏的作用中起不同的调节作用,更多药理试验结果显示,α7亚基在对烟碱引起心率降低的调节中起主要作用,β4亚基则在心率的增加过程中起主要作用。
Nicotinic acetylcholine receptors（nAchRs） are pentameric,typically being composed of α and β. To investigate which receptor subtype is active in the heart,we conducted a series of experiments using rat as model animal. Nicotine administration （100 μmol/L） caused a brief decrease -7±2% followed by a much larger increase 17±5M in heart rate and slowly returned to baseline within 10 to 15 min. The nicotine-induced decrease in heart rate could be abolished by an α7-specific antagonist, α-bungarotoxin （100 nmol/L）. In contrast, the nicotine-induced increase in heart rate persisted in the presence of α-bungarotoxin. To investigate which subunits may contribute to the nicotine-induced increase in heart rate,experiments repeated were with cytisine,an agonist at nAehRs that contain β4 subunits. The results were similar to those obtained with nicotine,suggesting that the nAChRs on sympathetic nerve terminals in the heart probably contain β4 subunits. The results of this study showed that pharmacologically distinct nAChRs are responsible for the differential effects of nicotine on heart rate. More specifically,our results suggested that α7 subunits participate in the initial nicotine-induced heart rate decrease, whereas β4 subunits helped to mediate the subsequent nicotine-induced increase in heart rate.
出处
《动物医学进展》
CSCD
2008年第1期39-42,共4页
Progress In Veterinary Medicine
