Premium
Characterisation of the Glycine Modulatory Site of the N ‐Methyl‐ d ‐Aspartate Receptor‐Ionophore Complex in Human Brain
Author(s) -
Procter A. W.,
Stratmann G. C.,
Francis P. T.,
Lowe S. L.,
Bertolucci P. H. F.,
Bowen D. M.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb02596.x
Subject(s) - glycine , glycine receptor , allosteric regulation , binding site , receptor , biochemistry , amino acid , nmda receptor , human brain , glutamic acid , chemistry , biology , stereochemistry , neuroscience
[ 3 H]Glycine binding and glycine modulation of [ 3 H]MK‐801 binding have been used to study the glycine allosteric site associated with the N ‐methyl‐D‐aspartate receptor complex in postmortem human brain. The effect of glycine on [ 3 H]MK‐801 binding appeared sensitive to duration of terminal coma, and possibly postmortem delay. Thirty percent of the binding occurred in a subfraction of brain tissue and did not show enhancement by glycine and glutamic acid. [ 3 H]Glycine binding to a subfraction free from this component was studied and showed high specific binding. K D and B max values showed considerable intersubject variability which did not appear to be due to demographic features or to tissue content of amino acids with an affinity for this site. The pharmacological characteristics of binding in this subfraction and a correlation between B max values and the maximal enhancement of [ 3 H]MK‐801 binding by glycine are consistent with [ 3 H]glycine binding occurring to an N ‐methyl‐D‐aspartate receptor complex associated site. Further support for this is provided by a significantly lower B max value for [ 3 H]glycine binding in subjects with Alzheimer's disease and reduced glycine enhancement of [ 3 H]MK‐801 binding. However, the effect of perimortem factors makes it difficult to confidently attribute this solely to a disease‐related change in the receptor. The possible role of the glycine allosteric site in the treatment of neuropsychiatric disorders is discussed.