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Paradoxical effects of 2‐amino‐4‐phosphonobutanoic acid and other 2‐amino‐ω‐phosphonoalkanoic acid on the n‐methyl‐d‐aspartate receptor ion channel
Author(s) -
Szabó Géza,
Horváth Edit J.,
Aráanyi Péter
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430280411
Subject(s) - nmda receptor , chemistry , glycine , amino acid , glutamic acid , stereochemistry , binding site , receptor , ion channel , glutamate receptor , non competitive inhibition , competitive binding , piperidine , biochemistry , enzyme
An extensively washed membrane preparation was used to measure the noncompetitive binding site of the N‐methyl‐D‐aspartate (NMDA) receptor complex with [ 3 H]‐1‐[1‐(2‐thienyl) cyclo‐hexyl] piperidine ([ 3 H]‐TCP). Addition of glutamic acid (Glu) or Glu + glycine (Gly) increased the binding of [ 3 H]‐TCP, reflecting that the NMDA receptor ion channel was opened by these compounds. [ 3 H]‐TCP binding was also increased by various 2‐amino‐ω‐phosphonoalkanoic (AP) compounds, of which 2‐amino‐4‐phosphonobutanoic acid (AP4) was the most effective. The effects of AP compounds were also observed in the presence of Gul. However, in the presence of Gly, or in the presence of Glu + Gly, 2‐amino‐5‐phosphonopentanoic acid (AP5) and 2‐amino‐7‐phosphonoheptanoic acid (AP7) inhibited the binding. The enhancing effect of AP4 was also inhibited by these compounds. Our conclusion is that AP compounds exert complex effects: they bind to and effect the NMDA receptor complex ion channel not only via the competitive binding site but may also interact with the potentiating Gly binding site. © Wiley‐Liss, Inc.