Catania M V, Hollingsworth Z, Penney J B, Young A B
Neurology Service, Massachusetts General Hospital, Boston 02114.
Neuroreport. 1993 Mar;4(3):311-3. doi: 10.1097/00001756-199303000-00021.
Metabotropic receptor subtypes have been proposed based on pharmacological, signal transduction and cDNA sequence data. We assessed potential metabotropic binding site subtypes with in vitro quantitative [3H]glutamate autoradiography in adult rat brains in the presence of saturating concentrations of N-methyl-D-aspartate (NMDA) and (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA). Quisqualate (QUIS) competition curves resolved two differentially distributed binding sites (KIhigh = 17 nM; KIlow = 62 microM). Trans-1-amino-cyclopentane- 1,3-dicarboxylic acid (t-ACPD) and 1S,3R-ACPD displaced [3H]glutamate binding both in the absence and presence of a quisqualate concentration (2.5 microM) that saturates the high affinity sites, suggesting that both sites are linked to metabotropic receptors. We conclude that two metabotropic binding sites with different distributions and pharmacological profiles can be detected with selective [3H]glutamate binding assays.
基于药理学、信号转导和cDNA序列数据，已提出了代谢型受体亚型。我们在成年大鼠脑中，于存在饱和浓度的N-甲基-D-天冬氨酸（NMDA）和（RS）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）的情况下，通过体外定量[3H]谷氨酸放射自显影评估了潜在的代谢型结合位点亚型。喹啉酸（QUIS）竞争曲线解析出两个分布不同的结合位点（KI高 = 17 nM；KI低 = 62 μM）。在不存在和存在使高亲和力位点饱和的喹啉酸浓度（2.5 μM）的情况下，反式-1-氨基环戊烷-1,3-二羧酸（t-ACPD）和1S,3R-ACPD均能取代[3H]谷氨酸结合，这表明这两个位点均与代谢型受体相关。我们得出结论，通过选择性[3H]谷氨酸结合测定法可检测到两个具有不同分布和药理学特征的代谢型结合位点。
