顺式-2,4-亚甲基谷氨酸是一种强效且具有选择性的N-甲基-D-天冬氨酸受体激动剂。

Cis-2,4-methanoglutamate is a potent and selective N-methyl-D-aspartate receptor agonist.

作者信息

Lanthorn T H, Hood W F, Watson G B, Compton R P, Rader R K, Gaoni Y, Monahan J B

机构信息

CNS Diseases Research, G.D. Searle & Co., St. Louis, MO.

出版信息

Eur J Pharmacol. 1990 Jul 17;182(3):397-404. doi: 10.1016/0014-2999(90)90036-6.

DOI:10.1016/0014-2999(90)90036-6

PMID:2146136

Abstract

Cis- and trans-2,4-methanoglutamate were compared with L-glutamate as acidic amino acid ligands. Cis-2,4-methanoglutamate had a Ki of 0.052 microM against N-methyl-D-aspartate (NMDA)-specific L-[3H]glutamate binding compared with 0.050 microM for L-glutamate. Cis-2,4-methanoglutamate exhibited no significant affinity against [3H]kainate or [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate ([3H]AMPA) binding. Trans-2,4-methanoglutamate had no significant affinity for any of these sites. Cis-2,4-methanoglutamate increased [3H]N-1[2-thienyl]cyclohexyl-3,4-piperidine [( 3H]TCP) binding with EC50 of 0.35 +/- 0.14 microM. It produced an inward current in rat brain mRNA-injected Xenopus oocytes which was blocked by the NMDA antagonist, D-2-amino-7-phosphonoheptanoate (D-AP7). Cis-2,4-methanoglutamate (EC50 = 15.9 microM) was 100-fold more potent than L-glutamate (EC50 = 1,584 microM) in reducing the excitatory postsynaptic potential in CA1 of hippocampal slices. Cis-2,4-methanoglutamate is the most potent, selective NMDA agonist known.

摘要

将顺式和反式-2,4-亚甲基谷氨酸作为酸性氨基酸配体与L-谷氨酸进行了比较。顺式-2,4-亚甲基谷氨酸对N-甲基-D-天冬氨酸（NMDA）特异性L-[3H]谷氨酸结合的Ki为0.052微摩尔，而L-谷氨酸为0.050微摩尔。顺式-2,4-亚甲基谷氨酸对[3H]海人藻酸或[3H]α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（[3H]AMPA）结合无明显亲和力。反式-2,4-亚甲基谷氨酸对这些位点均无明显亲和力。顺式-2,4-亚甲基谷氨酸使[3H]N-1-[2-噻吩基]环己基-3,4-哌啶（[3H]TCP）结合增加，EC50为0.35±0.14微摩尔。它在注射大鼠脑mRNA的非洲爪蟾卵母细胞中产生内向电流，该电流被NMDA拮抗剂D-2-氨基-7-膦酰庚酸（D-AP7）阻断。在降低海马切片CA1区兴奋性突触后电位方面，顺式-2,4-亚甲基谷氨酸（EC50 = 15.9微摩尔）的效力比L-谷氨酸（EC50 = 1584微摩尔）强100倍。顺式-2,4-亚甲基谷氨酸是已知最强效、最具选择性的NMDA激动剂。