Glutamate 와 Glycine 이 휜쥐 뇌의 N-Methyl-D-Aspartate 수용체에 대한 [3H]MK-801 결합반응에 미치는 영향

Effects of Glutamate and Glycine on the Binding of [3H]MK-801 to the N-Methyl-D-Aspartate Receptor in Rat Brain

In an attempt to investigate the characteristics of N-methyl-D-aspartate (NM D A ) authors receptor which is expected to play an important role in neuropsychiatric field recently, the author performed receptor binding assay using [3H]MK-801[( + ) —5 —methyl-10, 11-dihydro- 5H-dibenzo[a, d]-cycloheptene-5, 10-imine maleate], which is known to selectively antagonize the NM D A receptor in noncompetitive fashion, in order to observe the effects of glycine and glutamate on [3H]MK-801 binding to rat brain membranes. The results are summarized as follows ; 1) Glutamate and glycine enhanced the binding of [3H]MK-801 to rat brain membranes. 2) In inhibition experiment of [3H]MK-801 binding to rat brain membranes by unlabeled ( + ) — M K —801 and Mg++, glutamate and glycine did not affect IC 50 of unlabeled ( + ) _ MK- 801, but reduced that of Mg++. 3) Glutamate and glycine did not affect Bmax of [3H]MK-801 to rat brain membranes, but decreased Kd value of [3H]MK-801. In conclusion, these results indicate that glutamate and glycine activate the N M D A receptor through distinct recognition sites respectively which may be allosterically coupled, and the the enhancement of [3H]MK-801 binding produced by these amino acids may result from the increase of affinity for but not the change in Bmax of [3H]MK-801.