Characterization df a [3H]Glycine Recognition Site as a Modulatory Site of the N‐Methyl‐D‐Aspartate Receptor Complex

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Abstract
A [3H]glycine recognition site in rat brain synaptic plasma membranes (SPM) has been identified, having characteristics expected of a modulatory component of the N-methyl-D-aspartate receptor complex. Inculpation of SPM with [3H]glycine for 10 min at 2°C results in saturable, reversible binding with a KD of 0.234 μMand a Bmax of 9.18 pmol/mg. A pharmacological analysis of this binding site indicates that D-serine (Ki= 0.27 μM), D-alanine (Ki= 1.02 μM), and D-cycloserine (Ki= 2.33 /μM) are patent inhibitors of binding, whereas the corresponding L isomers have significantly less activity (Ki= 25.4 μM, 15.9 μM, and > 100 μM, respectively). Inactive at concentrations of up to 100 μM were strychnine, L-valine, N,N=-dimethylglycine, ami-nomethylphosphonate, and aminomethylsulfonate. The active compounds were analyzed further for their ability to stimulate [3H] l-[l-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) binding to Triton X-100-washed SPM. Results indicate that the affinity of the compounds for the [3H]glycine recognition site correlates with the ability of these analogues to stimulate (3H]TCP binding.