ω-芋螺毒素MVIIA和MVIIC对α9α10乙酰胆碱受体的活性研究

Activities of ω-conotoxin MVIIA and MVIIC on α9α10 Nicotinic Acetylcholine Receptor

分析和检测了ω-芋螺毒素MVIIA和MVIIC对α9α10乙酰胆碱受体(nAChR)的结合活性,并用重组表达在非洲爪蟾卵母细胞膜上的大鼠α9α10 nAChR受体,分别评价了2个ω-芋螺毒素MVIIA和MVIIC在常规的ND96灌流液和不含钙离子的钡离子ND96灌流液(Ba2+ND96)中对该受体的阻断活性.研究表明,2个ω-芋螺毒素MVIIA和MVIIC在Ba2+ND96灌流液中对α9α10 nAChR没有抑制作用,而它们在常规的ND96灌流液中却表现出微弱的抑制活性,这应是受钙离子激活产生的氯离子电流影响的结果.因此,2个ω-芋螺毒素MVIIA和MVIIC并不是α9α10 nAChR的有效阻断剂,其作用机理与α-芋螺毒素Vc1.1和Rg IA完全不同.本研究阐明了芋螺毒素抑制α9α10 nAChR和钙离子通道的机理,这对研发新型的芋螺毒素镇痛药和更好地治疗顽固性疼痛具有很重要的科学意义.

In the study,the combining activities of two ω-conotoxins,MVIIA and MVIIC on α 9 α10 nicotinic acetylcholine receptor（nAChR） were determined,and rat α9 α 10 nAChR expressed in Xenopus oocytes was used to evaluate blocking activities of the two ω-conotoxins,MVIIA and MVIIC,both in regular ND96 and Ba ＋＋ ND96 buffer,respectively.The results indicated that they failed to block α9 α10 nAChR in Ba ＋ ＋ ND96,but showed very weak potency to inhibit α9 α10 nAChR in regular ND96,which may be affected by Ca ＋ ＋ activated chloride currents.So,ω-conotoxins MVIIA and MVIIC are not effective antagonists of α9 α10 nAChR,and their mechanisms are different from that of-conotoxins Vc1.1 and Rg IA.Our findings elucidate how conotoxins inhibit α9 α10 nAChR and N-type voltage-gated calcium channels（VGCC）（Cav2.2）,and which is critical for developing these peptides into analgesics and provides better therapy protocl for pain.