Metergoline inhibits the neuronal Navl.2 voltage- dependent Na^＋ channels expressed in Xenopus oocytes  

作　　者：Jun-ho LEE Jian LIU Minkyu SHIN Moochang HONG Seung-yeol NAH Hyunsu BAE 

机构地区：[1]Department of Physiology, College of Korean Medicine, Kyung Hee University, Seou1130- 701, Republic of Korea [2]College of Veterinary Medicine, Konkuk University, Seou1130- 701, Republic of Korea

出　　处：《Acta Pharmacologica Sinica》2014年第7期862-868,共7页中国药理学报（英文版）

摘　　要：Aim： Metergoline is an ergot-derived psychoactive drug that acts as a ligand for serotonin and dopamine receptors. The aim of this study was to investigate the regulatory effects of metergoline on the neuronal Nav1.2 voltage-dependent Na^＋ channels in vitro. Methods： Xenopus oocytes were injected with cRNAs encoding rat brain Nav1.2 α and β1 subunits. Voltage-activated Na^＋ currents were recorded using two-electrode voltage clamp technique. Drugs were applied though perfusion. Results： Both metergoline and lidocaine reversibly and concentration-dependently inhibited the peak of Na^＋ currents with IC50 values of 3.6±4.2 and 916.9±98.8 μmol/L, respectively. Metergoline （3 pmol/L） caused a 6.8±1.2 mV depolarizing shift of the steady-state activation curve of the Na^＋ currents, and did not alter the inactivation curve. In contrast, lidocaine （3 μmol/L） caused a 12.7±1.2 mV hyperpolarizing shift of the inactivation curve of the Na^＋ currents without changing the steady-state activation curve. Both metergoline and lidocaine produced tonic and use-dependent inhibition on the peak of Na^＋ currents. Conclusion： Metergoline exerts potent inhibition on the activity of neuronal Nav1.2 channels, which may contribute to its actions on the central nervous system.Aim： Metergoline is an ergot-derived psychoactive drug that acts as a ligand for serotonin and dopamine receptors. The aim of this study was to investigate the regulatory effects of metergoline on the neuronal Nav1.2 voltage-dependent Na^＋ channels in vitro. Methods： Xenopus oocytes were injected with cRNAs encoding rat brain Nav1.2 α and β1 subunits. Voltage-activated Na^＋ currents were recorded using two-electrode voltage clamp technique. Drugs were applied though perfusion. Results： Both metergoline and lidocaine reversibly and concentration-dependently inhibited the peak of Na^＋ currents with IC50 values of 3.6±4.2 and 916.9±98.8 μmol/L, respectively. Metergoline （3 pmol/L） caused a 6.8±1.2 mV depolarizing shift of the steady-state activation curve of the Na^＋ currents, and did not alter the inactivation curve. In contrast, lidocaine （3 μmol/L） caused a 12.7±1.2 mV hyperpolarizing shift of the inactivation curve of the Na^＋ currents without changing the steady-state activation curve. Both metergoline and lidocaine produced tonic and use-dependent inhibition on the peak of Na^＋ currents. Conclusion： Metergoline exerts potent inhibition on the activity of neuronal Nav1.2 channels, which may contribute to its actions on the central nervous system.

关 键 词：metergoline ergot alkaloid ANTIDEPRESSANT Na^＋ channels Nav1.2 Xenopus oocyte LIDOCAINE 

分 类 号：Q332[生物学—遗传学] Q463