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 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 (< or =0.1 microM). 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.
Leewanich
Pathama
P
Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand. pathama@swu.ac.th
Tohda
Michihisa
M
Takayama
Hiromitsu
H
Sophasan
Samaisukh
S
Watanabe
Hiroshi
H
Matsumoto
Kinzo
K
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D018515:Plant Leaves; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000096:biosynthesis*; D014982:Xenopus laevis
D000470:Alkaloids; D016202:N-Methylaspartate; D010936:Plant Extracts; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor; C108901:corymine