神经元N受体功能失敏对M受体拮抗剂药理作用的影响

Effect on antagonism of muscarinic acetylcholine receptors antagonists by desensitization of nicotinic acetylcholine receptors

目的研究神经元N受体失敏对宾赛克嗪和阿托品拮抗M受体功能药理作用的影响。方法选用原代培养的大鼠颈上交感神经元为模型,以烟碱和氧化震颤素为工具药,选取拮抗剂对M受体介导的IM-抑制的拮抗作用为指标,采用膜片钳全细胞记录技术进行研究。结果与正常状态相比,在N受体失敏状态下,宾赛克嗪和阿托品对M受体功能的拮抗作用强度均减弱,且宾赛克嗪减弱的幅度小于阿托品。随着N受体逐渐从失敏状态恢复到正常状态,宾赛克嗪和阿托品对M受体功能的拮抗作用强度也呈逐渐恢复的趋势。结论 N受体失敏使M受体拮抗剂对M受体功能的拮抗作用强度减弱。

Aim To investigate the effect on antagonism of benthiactzine and atropine against the function of muscarinic acetylcholine receptors by desensitization of nicotinic acetylcholine receptors. Methods The whole cell recording configuration of patch-clamp technique was used and the cell model was rat SCG neurons. To identify antagonists＇ antimuscarinic effect, mAchRs mediated IM-inhibition was measured and nicotine and oxotremorine were used. Results After de sensitization of nAChRs,the antimuscarinic effect ofboth benthiactzine and atropine decreased compared to the normal condition. The decreased antimuscarinic effect of benthiactzine was weaker than that of atro-pine. The antimuscarinic effect of both benthiactzine and atropine recovered gradually with the recovery of nAChRs from desensitization. Conclusion Desensiti-zation of nAChRs weakens the antagonists＇ antimuscarinic effect.