Buller A L, Monaghan D T
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Eur J Pharmacol. 1997 Feb 5;320(1):87-94. doi: 10.1016/s0014-2999(96)00880-1.
The pharmacology of recombinant NR1a/NR2D NMDA receptors expressed in Xenopus oocytes was examined and compared to the pharmacology of NR1a/NR2A, NR1a/NR2B and NR1a/NR2C heteromers. The NR1/NR2D heteromer showed a pharmacological profile distinct from each of the other NR1/NR2 heteromers. This unique pharmacological profile was characterized by a relatively lower affinity for the agonist homoquinolinate and the antagonists 2-amino-5-phosphonopentanoate (D-AP5) and (R,E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (D-CPPene) but not for the antagonists (+/-)-4-(4-phenylbenzoyl) piperazine-2,3-dicarboxylic acid (PBPD) and alpha-amino-5-(phosphonomethyl)[1,1'-biphenyl]-3-propanoic acid (EAB515). NR2D-containing receptors displayed a pharmacological profile most similar to that observed for receptors containing the genetically related NR2C subunit. These findings parallel observations obtained for native NMDA receptors in the medial thalamus (presumed to contain NR2D subunits) and forebrain (presumed to contain NR2A and NR2B subunits). Thus, only compounds that discriminate between either NR2A- or NR2B-containing heteromers and NR2D-containing heteromers also discriminate between forebrain and medial thalamic NMDA receptors. While the pharmacology of the NR1a/NR2D receptor shows many parallels to the medial thalamic NMDA receptor, some differences were observed. Certain compounds which discriminate between medial thalamic and cerebellar (presumed to contain NR2C subunits) receptors (e.g., homoquinolinate, D-CPPene) did not show a similar selectivity for NR1a/NR2D receptors relative to NR1/NR2C receptors. Co-expression of NR1a, NR2B and NR2D subunits in Xenopus oocytes resulted in the formation of heteromeric complexes with unique pharmacological properties, suggesting the co-existence of these two distinct NR2 subunits in the same receptor complex.
对非洲爪蟾卵母细胞中表达的重组NR1a/NR2D NMDA受体的药理学特性进行了研究，并与NR1a/NR2A、NR1a/NR2B和NR1a/NR2C异聚体的药理学特性进行了比较。NR1/NR2D异聚体表现出与其他NR1/NR2异聚体不同的药理学特征。这种独特的药理学特征表现为对激动剂高喹啉酸以及拮抗剂2-氨基-5-膦酰基戊酸（D-AP5）和（R,E）-4-（3-膦酰基-2-丙烯基）哌嗪-2-羧酸（D-CPPene）的亲和力相对较低，但对拮抗剂（±）-4-（4-苯基苯甲酰基）哌嗪-2,3-二羧酸（PBPD）和α-氨基-5-（膦酰基甲基）[1,1'-联苯]-3-丙酸（EAB515）的亲和力并非如此。含NR2D的受体表现出与含遗传相关NR2C亚基的受体最为相似的药理学特征。这些发现与在内侧丘脑（推测含有NR2D亚基）和前脑（推测含有NR2A和NR2B亚基）中对天然NMDA受体的观察结果一致。因此，只有能够区分含NR2A或NR2B的异聚体与含NR2D的异聚体的化合物，才能区分前脑和内侧丘脑的NMDA受体。虽然NR1a/NR2D受体的药理学特性与内侧丘脑NMDA受体有许多相似之处，但也观察到了一些差异。某些能够区分内侧丘脑和小脑（推测含有NR2C亚基）受体的化合物（如高喹啉酸、D-CPPene），相对于NR1/NR2C受体，对NR1a/NR2D受体并未表现出类似的选择性。在非洲爪蟾卵母细胞中共表达NR1a、NR2B和NR2D亚基，导致形成具有独特药理学特性的异聚体复合物，这表明这两种不同的NR2亚基共存于同一受体复合物中。
