α3β2与α3β4烟碱型乙酰胆碱受体α和β亚基不同配比的药理活性研究

发布时间：2019-01-06 16:13

【摘要】：目的:比较α和β亚基不同配比形成α3β2和α3β4烟碱型乙酰胆碱受体(nAChR)敏感性的差异。方法:体外转录获得α和β亚基的cRNA,采用显微注射将3种不同配比(α∶β分别为1∶10、1∶1和10∶1)的cRNA注入非洲爪蟾卵母细胞,利用双电极电压钳检测受体表达情况。利用激动剂乙酰胆碱(ACh)和拮抗剂α-芋螺毒素Reg IIA(α-CTx Reg IIA)检测在3种配比条件下形成受体药理活性的差异。结果:对于α3β2 nAChR亚型,在3种配比情况下,ACh的半数有效浓度(EC50)分别为91.2μmol/L、104.4μmol/L和130.6μmol/L,α-CTx Reg IIA的半数抑制浓度(IC50)分别为40.2 nmol/L、36.4 nmol/L和42.3 nmol/L。对于α3β4 nAChR亚型,在3种配比情况下,ACh的EC50分别为44.0μmol/L、110.0μmol/L和230.0μmol/L,α-CTx Reg IIA的IC50分别为226.8 nmol/L、71.5 nmol/L和49.4 nmol/L。结论:α3和β4亚基比例的改变会导致α3β4 nAChR结构和药理活性的改变。α3和β2亚基比例的改变对α3β2 nAChR结构和活性没有影响。
[Abstract]:Aim: to compare the sensitivity of 伪 3 尾 2 and 伪 3 尾 4 nicotinic acetylcholine receptor (nAChR) to 伪 3 尾 2 and 伪 3 尾 subunits. Methods: cRNA, of 伪 and 尾 subunits obtained by transcription in vitro were injected into Xenopus laevis oocytes with three different ratios (伪: 尾 = 1: 10: 1: 1: 1 and 10:1) by microinjection. The expression of receptor was detected by double electrode voltage clamp. Agonist acetylcholine (ACh) and antagonist 伪 -Conotoxin Reg IIA (伪 CTx Reg IIA) were used to detect the difference of pharmacological activity of the receptors formed under three conditions. Results: for 伪 3 尾 2 nAChR subtype, the half effective concentration (EC50) of ACh was 91.2 渭 mol/L,104.4 渭 mol/L and 130.6 渭 mol/L, 伪 -CTx Reg IIA was 40.2 nmol/L, respectively. 36.4 nmol/L and 42.3 nmol/L. For 伪 3 尾 4 nAChR subtype, the EC50 of ACh is 44.0 渭 mol/L,110.0 渭 mol/L and 230.0 渭 mol/L, 伪 -CTx Reg IIA IC50 is 226.8 nmol/L,71.5 nmol/L and 49.4 nmol/L., respectively. Conclusion: the ratio of 伪 3 and 尾 4 subunits may lead to the change of the structure and pharmacological activity of 伪 3 尾 4 nAChR, but the ratio of 伪 3 and 尾 2 subunits has no effect on the structure and activity of 伪 3 尾 2 nAChR.
【作者单位】：海南大学热带生物资源教育部重点实验室海口市海洋药物重点实验室海洋学院药学系;
【基金】：国家自然科学基金重点国际合作项目(No.81420108028);国家自然科学基金资助项目(No.41366002) 长江学者和创新团队发展计划项目(No.IRT-15R15) 海南省高等学校科学研究项目(No.Hnky2017-16) 海南大学科研启动基金资助项目[No.KYQD(ZR)1713
【分类号】：R96

【相似文献】