NMDA receptor modulation by a brain endogenous factor (Endobain E): effects of zinc, spermidine and pH

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

Palm Beach, Miami, USA

Congreso; American Society for Neurochemistry (ASN); 2002

A brain endogenous factor, termed endobain E, allosterically modulates NMDA receptor, an effect dependent on receptor activation by Glutamate (Glu) and Glycine (Gly). In the present study, competitive 3H dizocilpine binding assays to brain membranes were carried out in a medium containing 10-5 Glu plus 10-8 Gly to analyze potential zinc, spermidine and pH influence on endobain E effect. A non-additive effect was recorded in the simultaneous presence of IC 25 Zn and endobain E in a concentration which inhibits 25 % 3H dizocilpine binding. With an endobain E concentration which decreases 25 % ligand binding, 10-8 – 10-2 SPD potentiated binding but failed to modify endobain E effect. 3H dizocilpine binding reduction by higher endobain E concentration was altered by 10-3 SPD. Additive effects were observed with IC 25 SPD site antagonists, either competitive or not competitive plus endobain E concentration which decreases binding 25 %. However, no additive or partially additive effects were respectively recorded with IC 50 arcaine or ifenprodil in the presence of an endobain concentration which decreases binding 50 %. When pH influence was tested, endobain E (70 mg original tissue) decreased 3H dizocilpine binding at pH 7.4 or 8.0 but 90 % at pH 6.5. Our results indicate that endobain E effect is interfered by Zn, modified by proton concentration and independent of NMDA receptor activation by SPD; this factor seems not to interact at polyamine site.