Characterization of a [3H]glycine recognition site as a modulatory site of the N-methyl-D-aspartate receptor complex.
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. Incubation of SPM with [3H]glycine for 10 min at 2 degrees C results in saturable, reversible binding with a KD of 0.234 microM and a Bmax of 9.18 pmol/mg. A pharmacological analysis of this binding site indicates that D-serine (Ki = 0.27 microM), D-alanine (Ki = 1.02 microM), and D-cycloserine (Ki = 2.33 microM) are potent inhibitors of binding, whereas the corresponding L isomers have significantly less activity (Ki = 25.4 microM, 15.9 microM, and greater than 100 microM, respectively). Inactive at concentrations of up to 100 microM were strychnine, L-valine, N,N-dimethylglycine, aminomethylphosphonate, and aminomethylsulfonate. The active compounds were analyzed further for their ability to stimulate [3H]1-[1-(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.
Monahan
J B
JB
Searle Research and Development, Division of G. D. Searle & Co., St. Louis, Missouri 63198.
Corpus
V M
VM
Hood
W F
WF
Thomas
J W
JW
Compton
R P
RP
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism*; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D013570:Synaptic Membranes / Q000378:metabolism; D014316:Tritium
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D014316:Tritium; C012058:tenocyclidine; D010622:Phencyclidine; D005998:Glycine