A brain endogeneous factor allosterically modulates [3H]dizocilpine binding: dependence on NMDA receptor activation by glutamate and glycine but not by spermidine

REINÉS A; ZÁRATE SANDRA; PEÑA C; RODRÍGUEZ DE LORES ARNAIZ G.

San Francisco, California, USA

Congreso; XIVth World Congress of Pharmacology, IUPHAR; 2002

A endogenous Na K ATPase inhibitor isolated from rat brain, endobain E, allosterically decreases 3H dizocilpine binding to cerebral cortex NMDA receptor. To further analyze endobain E effect, competitive 3H dizocilpine binding assays with different incubation media were carried out. No additive effects were observed with endobain E concentration which decreases binding 25 % plus IC 25 Zn or IC 25 competitive antagonists for Glu (Glutamate) or Gly (Glycine) sites. In the presence of endobain E with Glu plus Gly at 10-8M concentration, 3H dizocilpine binding was 84 % of control, whereas with Glu plus Gly at 10-5 M concentration, it decreased to 53 %. With an endobain E concentration which decreases 25 % ligand binding, 10-8 – 10-2 SPD potentiated binding but failed to modify endobain E effect. Additive effects were observed with IC 25 SPD site antagonists, either competitive or not competitive plus endobain E concentration which decreases binding 25 %. Thus, endobain E effect is dependent on NMDA receptor activation by Glu and Gly but not by SPD; this factor seems not to interact at polyamine site.