Amphetamine inhibits the
N-methyl-D-aspartate
receptor-mediated responses by directly
interacting with the receptor/channel
complex
葉健全
Yeh;G.C.;Chen;J.C.;Tsai;H.C.;Wu;H.H.;Lin;C.Y.;Hsu;P.C.;and
Peng;Y.C.
摘要
Abstract
neurotransmission. However, the involvement of the N-methyl-D-aspartate (NMDA) receptor in AMPH-induced neuropathology is also known. Recent investigation has found that high concentration of dopamine could inhibit NMDA receptor-mediated responses by blocking the NMDA receptor channel. By virtue of the structure similarity between dopamine and AMPH, we
determined whether d-AMPH and its analogs, l-AMPH and methamphetamine (MAMH), could affect the NMDA receptormediated
[3H]N-[1-(2-thienyl)cyclohexyl] piperidine ([3H]TCP) binding in rat cortical membrane preparations and intracellular 45Ca2 accumulation and cell death
in the rat primary cortical cell cultures. AMPH concentration-dependently inhibited NMDA- and glycine-stimulated [3H]TCP binding and intracellular
45Ca2 accumulation with two distinct potencies; a minor inhibition with high potency and a major inhibition with low potency. [3H]TCP binding suggested that the high-potency inhibition was produced by decreasing agonist-induced activation of the NMDA receptor channel. On the other hand, the low-potency inhibition was produced by competing with [3H]TCP binding in the NMDA receptor channel, like the action of noncompetitive antagonist of the NMDA receptor. However, AMPH analogs were less potent in inhibiting NMDA- and glycine- induced cultured cell death. Thus, this result indicates that AMPH
could antagonize the NMDA receptor-mediated responses in vitro by two different mechanisms, probably, through directly interacting with two distinct sites on this receptor/ channel complex.
