Spermidine and pH effect on NMDA receptor modulation by an endogenous factor

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

Ciudad de Corrientes

Congreso; XXXIII Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); 2001

A brain endogenous factor, Endobain E, allosterically modulates NMDA receptor, an effect dependent on receptor activation by glutamate (Glu) and Glycine (Gly). To analyze potential spermidine (SPD) and pH action on Endobain effect competitive 3H MK-801binding assays to brain membranes were carried out with 10-5 Glu and 10-8 Gly with an Endobain concentration wich decreased 25 % 3H MK-801binding. 10-2 – 10-8 SPD potentiated ligand binding but failed to modify Endobain E effect. 3H MK-801binding reduction by higher Endobain E concentrations was unaltered by 10-3 M SPD addition. Additive effects were observed with IC 25 competitive (arcaine) or non-competitive (ifenprodil) SPD site antagonists plus an Endobain 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 %. Endobain E decreases 3H MK-801binding 25 % at pH 7.4 or 8.0 but 90 % at pH 6.5. Results indicate that endobain e effect is independent of NMDA receptor activation by SPD but modified by proton concentration; this factor seems not to interact at polyamine site.