Corymine Potentiates NMDA-Induced Currents in Xenopus Oocytes Expressing NR1a/NR2B Glutamate Receptors

Previous studies demonstrated that corymine, an indole alkaloid isolated from the leaves of Hunter zeylanica, dose-dependently inhibited strychnine-sensitive glycine-induced currents. However, it is unclear whether this alkaloid can modulate the function of the N-methyl-D-aspartate (NMDA) receptor o...

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Main Authors: Pathama Leewanich, Michihisa Tohda, Hiromitsu Takayama, Samaisukh Sophasan, Hiroshi Watanabe, Kinzo Matsumoto
Format: Article
Language:English
Published: Elsevier 2005-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319322157
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author Pathama Leewanich
Michihisa Tohda
Hiromitsu Takayama
Samaisukh Sophasan
Hiroshi Watanabe
Kinzo Matsumoto
author_facet Pathama Leewanich
Michihisa Tohda
Hiromitsu Takayama
Samaisukh Sophasan
Hiroshi Watanabe
Kinzo Matsumoto
author_sort Pathama Leewanich
collection DOAJ
description Previous studies demonstrated that corymine, an indole alkaloid isolated from the leaves of Hunter zeylanica, dose-dependently inhibited strychnine-sensitive glycine-induced currents. However, it is unclear whether this alkaloid can modulate the function of the N-methyl-D-aspartate (NMDA) receptor on which glycine acts as a co-agonist via strychnine-insensitive glycine binding sites. This study aimed to evaluate the effects of corymine on NR1a/NR2B NMDA receptors expressed in Xenopus oocytes using the two-electrode voltage clamp technique. Corymine significantly potentitated the NMDA-induced currents recorded from oocytes on days 3 and 4 after cRNA injection but it showed no effect when the current was recorded on days 5 and 6. The potentiating effect of corymine on NMDA-induced currents was induced in the presence of a low concentration of glycine (≤0.1 µM). Spermine significantly enhanced the potentiating effect of corymine observed in the oocytes on days 3 and 4, while the NMDA-receptor antagonist 2-amino-5-phosphonopentanone (AP5) and the NMDA-channel blocker 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) reversed the effect of corymine. On the other hand, the nonspecific chloride channel blocker 4,4-di-isothiocyano stilbene-2,2-disulfonoc acid (DIDS) had no effect on the corymine potentiation of NMDA currents. There was no good correlation between corymine- and spermine-induced potentiation of the NMDA-current response in Xenopus oocytes. These results suggest that corymine potentiates the NMDA-induced currents by interacting with a site different from the spermine binding site. Keywords:: corymine, potentiating effect, NR1a/NR2B NMDA receptor, Xenopus oocyte
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spelling doaj.art-f1e95ec7fb9d40ec88241f4ea0f7134b2022-12-22T03:04:57ZengElsevierJournal of Pharmacological Sciences1347-86132005-01-019815865Corymine Potentiates NMDA-Induced Currents in Xenopus Oocytes Expressing NR1a/NR2B Glutamate ReceptorsPathama Leewanich0Michihisa Tohda1Hiromitsu Takayama2Samaisukh Sophasan3Hiroshi Watanabe4Kinzo Matsumoto5Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand; Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand; Corresponding author (affiliation #1). FAX: +662-260-2122, ext. 4013 E-mail: pathama@swu.ac.thDivision of Medicinal Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, JapanLaboratory of Molecular Structure and Biological Function, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, JapanDepartment of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, ThailandDivision of Medicinal Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, JapanDivision of Medicinal Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, JapanPrevious studies demonstrated that corymine, an indole alkaloid isolated from the leaves of Hunter zeylanica, dose-dependently inhibited strychnine-sensitive glycine-induced currents. However, it is unclear whether this alkaloid can modulate the function of the N-methyl-D-aspartate (NMDA) receptor on which glycine acts as a co-agonist via strychnine-insensitive glycine binding sites. This study aimed to evaluate the effects of corymine on NR1a/NR2B NMDA receptors expressed in Xenopus oocytes using the two-electrode voltage clamp technique. Corymine significantly potentitated the NMDA-induced currents recorded from oocytes on days 3 and 4 after cRNA injection but it showed no effect when the current was recorded on days 5 and 6. The potentiating effect of corymine on NMDA-induced currents was induced in the presence of a low concentration of glycine (≤0.1 µM). Spermine significantly enhanced the potentiating effect of corymine observed in the oocytes on days 3 and 4, while the NMDA-receptor antagonist 2-amino-5-phosphonopentanone (AP5) and the NMDA-channel blocker 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) reversed the effect of corymine. On the other hand, the nonspecific chloride channel blocker 4,4-di-isothiocyano stilbene-2,2-disulfonoc acid (DIDS) had no effect on the corymine potentiation of NMDA currents. There was no good correlation between corymine- and spermine-induced potentiation of the NMDA-current response in Xenopus oocytes. These results suggest that corymine potentiates the NMDA-induced currents by interacting with a site different from the spermine binding site. Keywords:: corymine, potentiating effect, NR1a/NR2B NMDA receptor, Xenopus oocytehttp://www.sciencedirect.com/science/article/pii/S1347861319322157
spellingShingle Pathama Leewanich
Michihisa Tohda
Hiromitsu Takayama
Samaisukh Sophasan
Hiroshi Watanabe
Kinzo Matsumoto
Corymine Potentiates NMDA-Induced Currents in Xenopus Oocytes Expressing NR1a/NR2B Glutamate Receptors
Journal of Pharmacological Sciences
title Corymine Potentiates NMDA-Induced Currents in Xenopus Oocytes Expressing NR1a/NR2B Glutamate Receptors
title_full Corymine Potentiates NMDA-Induced Currents in Xenopus Oocytes Expressing NR1a/NR2B Glutamate Receptors
title_fullStr Corymine Potentiates NMDA-Induced Currents in Xenopus Oocytes Expressing NR1a/NR2B Glutamate Receptors
title_full_unstemmed Corymine Potentiates NMDA-Induced Currents in Xenopus Oocytes Expressing NR1a/NR2B Glutamate Receptors
title_short Corymine Potentiates NMDA-Induced Currents in Xenopus Oocytes Expressing NR1a/NR2B Glutamate Receptors
title_sort corymine potentiates nmda induced currents in xenopus oocytes expressing nr1a nr2b glutamate receptors
url http://www.sciencedirect.com/science/article/pii/S1347861319322157
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