Specific blockade of muscle acetylcholine receptor by α-conotoxin MIA and MIB
10.16438/j.0513-4870.2021-1434
- VernacularTitle:α-芋螺毒素MIA和MIB特异性阻断肌肉型乙酰胆碱受体研究
- Author:
Xi-xi WU
1
;
Liu-jun WANG
1
;
Xiao-peng ZHU
2
;
Dong-ting ZHANGSUN
1
;
Yong WU
2
;
Su-lan LUO
1
,
3
Author Information
1. Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China
2. School of Medicine, Guangxi University, Nanning 530004, China
3. School of Medicine, Guangxi University, Nanning 530004, China
- Publication Type:Research Article
- Keywords:
italic>Conus magus;
italic>α-conotoxin;
solid phase synthesis of 9-fluorene methoxycarbonyl;
oxidative folding;
muscle type nAChRs;
molecular docking
- From:
Acta Pharmaceutica Sinica
2022;57(3):724-730
- CountryChina
- Language:Chinese
-
Abstract:
The α-conotoxins are peptide toxins that are identified from the venom of marine cone snails and they hold outstanding potency on various subtypes of nicotinic acetylcholine receptors (nAChRs). nAChRs have an important role in regulating transmitter release, cell excitability, and neuronal integration, so nAChR dysfunctions have been involved in a variety of severe pathologies. Four types of α-3/5 conotoxins MI, MIA, MIB and MIC have been found from Conus magus. Among them, the activity and selectivity of MIA and MIB have not been well studied. In this study, four α-3/5 conotoxins MI, MIA, MIB and MIC were synthesized by solid peptide synthesis method, and the bioactivities of them were screened by double electrode voltage clamp electrophysiology. The results showed that MIA and MIB selectively inhibited muscle type acetylcholine receptors with IC50 values of 14.45 and 72.78 nmol·L-1, respectively, which are slightly weaker than MI and MIC. Molecular docking results have shown MIA and MIB interact with muscle-type nAChRs with similar mechanism. The reasons for activity differences may relate to the size of the N-terminal amino acids. Together, the conotoxins MIA and MIB may have the potential to develop as a tool for detect the function of muscle type nAChRs, as well as the diagnosis or treat of related diseases.
