PT  - JOURNAL ARTICLE
AU  - J B Monahan
AU  - W F Hood
AU  - J Michel
AU  - R P Compton
TI  - Effects of guanine nucleotides on N-methyl-D-aspartate receptor-ligand interactions.
DP  - 1988 Aug 01
TA  - Molecular Pharmacology
PG  - 111--116
VI  - 34
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/34/2/111.short
4100  - http://molpharm.aspetjournals.org/content/34/2/111.full
SO  - Mol Pharmacol1988 Aug 01; 34
AB  - Guanine nucleotides have been examined as to their effects on subclass-specific excitatory amino acid receptor-ligand interactions. Guanine nucleotides selectively inhibit L-[3H]glutamate binding to the N-methyl-D-aspartate (NMDA) recognition site while showing a lesser effect on [3H]kainate, [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and sodium-dependent L-[3H]glutamate binding. Of the series of guanine nucleotides tested in the inhibition of NMDA-specific L-[3H]glutamate binding, GTP, GDP, 5'-guanylylimidodiphosphate and 5'-guanylylmethylenediphosphate were significantly more potent than GMP, cyclic GMP and guanosine. Scatchard analysis indicates that the GTP inhibition (IC50 = 28 microM) of this NMDA-specific L-[3H]glutamate binding results from a decrease in the affinity of L-glutamate for the NMDA receptor whereas no alteration in the number of binding sites is observed. A kinetic analysis indicates that this decrease in affinity may be attributed to a decrease in association rate whereas no change in dissociation rate is observed. GTP (25 microM) lowers the affinities of both NMDA agonists (NMDA, L-glutamate, L-aspartate, and L-homocysteate) and antagonists (D-2-amino-5-phosphonovalerate, D-2-amino-7-phosphonoheptanoate, and D-2-aminoadipate). Pretreatment of the synaptic plasma membranes with either pertussis or cholera toxin had no significant effect on the GTP inhibition of NMDA-specific L-[3H] glutamate binding. The data suggest that guanine nucleotides can negatively modulate the NMDA receptor; however, the mechanism of this modulation is unclear.