Ransom R W, Deschenes N L
Merck Sharp and Dohme Research Laboratories, West Point, PA 19486.
Eur J Pharmacol. 1988 Oct 26;156(1):149-55. doi: 10.1016/0014-2999(88)90157-4.
Kynurenic acid (KYN) non-competitively inhibited N-methyl-D-aspartate (NMDA)-induced [3H]norepinephrine ([3H]NE) release from rat hippocampal slices. At 100 microM KYN, the effect on release was primarily on the maximal obtainable response to NMDA. Glycine was able to completely block the inhibitory effects of 100 microM KYN on NMDA-evoked release. This ability to prevent KYN inhibition of release was shared by other amino acids with the following order of potency: glycine greater than D-serine greater than D-alanine much greater than L-serine greater than or equal to L-alanine. Neither isomer of valine or threonine was able to reverse KYN inhibition of NMDA-induced release. These potencies agreed with the relative abilities of these amino acids to displace strychnine-insensitive [3H]glycine binding to rat brain membranes. Glycine and D-serine had no effect on the inhibition of NMDA-stimulated [3H]NE release produced by D-2-amino-5-phosphonovaleric acid, MK-801 or Mg2+. Also, neither amino acid modified KYN inhibition of kainic acid-induced release. These data demonstrate that the glycine regulatory site associated with the NMDA receptor can be demonstrated in whole brain slices by using an antagonist to attenuate the influences of endogenous glycine.
犬尿氨酸（KYN）非竞争性抑制N-甲基-D-天冬氨酸（NMDA）诱导的大鼠海马切片中[3H]去甲肾上腺素（[3H]NE）的释放。在100微摩尔KYN时，其对释放的影响主要作用于对NMDA的最大可获得反应。甘氨酸能够完全阻断100微摩尔KYN对NMDA诱发释放的抑制作用。其他氨基酸也具有阻止KYN抑制释放的能力，其效力顺序如下：甘氨酸＞D-丝氨酸＞D-丙氨酸＞＞L-丝氨酸≥L-丙氨酸。缬氨酸或苏氨酸的任何一种异构体都不能逆转KYN对NMDA诱导释放的抑制作用。这些效力与这些氨基酸取代大鼠脑膜上士的宁不敏感的[3H]甘氨酸结合的相对能力一致。甘氨酸和D-丝氨酸对D-2-氨基-5-磷酸缬氨酸、MK-801或Mg2+所产生的NMDA刺激的[3H]NE释放的抑制作用没有影响。此外，这两种氨基酸都未改变KYN对 kainic 酸诱导释放的抑制作用。这些数据表明，通过使用拮抗剂减弱内源性甘氨酸的影响，可以在全脑切片中证明与NMDA受体相关的甘氨酸调节位点。
