Monoamines directly inhibit N-methyl-D-aspartate receptors expressed in Xenopus oocytes in a voltage-dependent manner.
Dopamine has numerous functions in the brain and has been shown to modulate responses of N-methyl-D-aspartate (NMDA) receptors on thalamic and hippocampus neurons [N.G. Castro, M.C.F. de Mello, F.G. de Mello, Y. Aracava, Direct inhibition of the N-methyl-D-aspartate receptor channel by dopamine and (+)-SKF38393, Br. J. Pharmacol. 126 (1999) 1847-1855]. Thus, the effects of dopamine, serotonin, tyramine, epinephrine, norepinephrine, and octopamine on NMDA receptors were studied using voltage-clamp recording of recombinant NMDA receptors expressed in Xenopus oocytes. Serotonin and tyramine, in addition to dopamine, were found to inhibit macroscopic currents at heteromeric NMDA receptors, but not AMPA (GluR1/GluR2) receptors. Epinephrine, norepinephrine and octopamine also weakly inhibited macroscopic currents at NR1/NR2A and NR1/NR2B receptors. The inhibitory effects of these monoamines became prominent at -100 mV comparing those at -20 mV. Mutations at NR1 N616, NR2B N615, and NR2B N616, but not at NR1 W563 and NR1 N650, reduced the inhibitory effects by monoamines. These results indicate that these monoamines directly act on the narrowest region of channel pore.
Masuko
Takashi
T
College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
Suzuki
Ikuko
I
Kizawa
Yasuo
Y
Kusama-Eguchi
Kuniko
K
Watanabe
Kazuko
K
Kashiwagi
Keiko
K
Igarashi
Kazuei
K
Kusama
Tadashi
T
D000818:Animals; D015306:Biogenic Monoamines / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D015640:Ion Channel Gating / Q000187:drug effects*; D016296:Mutagenesis / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D014982:Xenopus laevis
D015306:Biogenic Monoamines; D016194:Receptors, N-Methyl-D-Aspartate