Characterisation of the binding of [3H]MDL 105,519, a radiolabelled antagonist for the N-methyl-D-aspartate-associated glycine site, to pig cortical brain membranes.

Binding of [3H]MDL 105,519 to glycine sites on N-methyl-D-aspartate (NMDA) receptors of pig cortical brain membranes was evaluated. [3H]MDL 105,519 labelled a homogeneous population of binding sites with a Kd-value of 3.73 +/- 0.43 nM and a Bmax-value of 3030 +/- 330 fmol/mg protein. Clear correlations between the affinity (Ki) to [3H]MDL 105,519 labelled sites and the potency (EC50) to enhance or inhibit non-equilibrium [3H]MK-801 binding in the nominal absence of glycine were shown for a variety of glycine site agonists, partial agonists and antagonists. The ratio of Ki to EC50 was >1 for agonists and partial agonists and <1 for antagonists. Various cations as well as glutamate and polyamine site ligands were shown to be able to influence [3H]MDL 105,519 binding to pig cortical brain membranes substantially.