In vitro and in vivo characterization of the NMDA receptor-linked strychnine-insensitive glycine site

• Published in: Epilepsy research Vol. 12; no. 2; pp. 157 - 162
• Main Authors: Peeters, B.W.M.M., Vanderheyden, P.M.L.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 01.07.1992; Elsevier
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; 7-Chlorokynurenic acid; [ 3H]MK801 binding; Animals; Animals, Newborn - metabolism; Biochemistry and metabolism; Biological and medical sciences; Central nervous system; d/ l-serine; Dizocilpine Maleate - metabolism; Fundamental and applied biological sciences. Psychology; Glycine - physiology; Kynurenic Acid - analogs & derivatives; Kynurenic Acid - pharmacology; Male; Neonatal convulsions; NMDA receptor; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - metabolism; Seizures - drug therapy; Seizures - metabolism; Serine - pharmacology; Stereoisomerism; Strychnine - pharmacology; Strychnine-insensitive glycine site; Vertebrates: nervous system and sense organs; 7-Chlorokynurenic acid; NMDA receptor; Neonatal convulsions; Strychnine-insensitive glycine site; d/ l-serine; [ 3H]MK801 binding; Characterization; Site; In vivo; Animal; Modulation; Central nervous system; Glycine; In vitro; Neurotransmission; Brain (vertebrata)
• DOI: 10.1016/0920-1211(92)90036-S
• ISSN: 0920-1211

Modulation of the NMDA receptor by the strychnine-insensitive glycine site was studied both in vitro and in vivo. In vitro the glycinergic stimulation of [ 3H]MK801 binding was measured in three different rat forebrain membrane preparations. An increased association rate of [ 3H]MK801 in the presence of glycine was observed. The binding of the radioligand was also enhanced by d-serine, whereas l-serine was less potent. The concentration-effect curves were shifted to the right by the glycine antagonist 7-chlorokynurenic acid (7CKA). In vivo modulation of the N- methyl- d-aspartate (NMDA) receptor was studied using NMDA induced convulsions in 7 day old rats. The NMDA effect was blocked by (+)-5-methyl-10,11-dihydro- 5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK801) and d-(-)-2-amino-5-phosphono-pentanoic acid (AP5). The effect of a submaximal dose of NMDA was dose-dependently potentiated by 1–10 mg/kg d-serine, whereas higher doses of l-serine were needed to obtain a similar effect. 7CKA did not affect NMDA-induced convulsions but reduced the d-serine potentiation of NMDA responses. This study illustrates the ability of the strychnine-insensitive glycine site to modulate the NMDA receptor function both in vitro and in vivo.