MCCG和MAP4在人代谢型谷氨酸受体亚型mGluR1b、mGluR2和mGluR4a上的药理学特性
Pharmacological characterization of MCCG and MAP4 at the mGluR1b, mGluR2 and mGluR4a human metabotropic glutamate receptor subtypes.
作者信息
Knöpfel T, Lukic S, Leonard T, Flor P J, Kuhn R, Gasparini F
机构信息
CNS Research, Pharmaceuticals Division, Ciba, Basle, Switzerland.
出版信息
Neuropharmacology. 1995 Aug;34(8):1099-102. doi: 10.1016/0028-3908(95)00111-i.
The two reported metabotropic glutamate receptor (mGluR) antagonists, alpha-methyl-cyclopropyl glycine (MCCG) and alpha-methyl-aminophosphonobutyrate (MAP4) were tested on the mGluR1b, mGluR2 and mGluR4a subtypes of human mGluRs. Neither MCCG (500 microM) nor MAP4 (500 microM) antagonized the activation of mGluR1b by 10 microM quisqualate. MCCG was found to potently antagonize the action of 30 microM (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] at mGluR2 (IC50 = 87.5 microM; apparent Kd = 25 microM) but did not block the action of 1 microM S-2-amino-4-phosphonobutyric acid at mGluR4a (IC50 >> 1 mM). MAP4 was found to be a weak antagonist or partial agonist at mGluR4a (IC50 > 500 microM) and, less potently, also antagonized the action of 30 microM (1S,3R)-ACPD) at mGluR2 (IC50 approximately 2 mM).
对两种已报道的代谢型谷氨酸受体（mGluR）拮抗剂α-甲基环丙基甘氨酸（MCCG）和α-甲基氨基膦酸丁酸（MAP4）进行了针对人mGluR的mGluR1b、mGluR2和mGluR4a亚型的测试。500微摩尔的MCCG和500微摩尔的MAP4均未拮抗10微摩尔喹啉酸对mGluR1b的激活作用。研究发现，MCCG能有效拮抗30微摩尔（1S,3R）-1-氨基环戊烷-1,3-二羧酸[（1S,3R）-ACPD]对mGluR2的作用（IC50 = 87.5微摩尔；表观解离常数Kd = 25微摩尔），但不阻断1微摩尔S-2-氨基-4-膦酸丁酸对mGluR4a的作用（IC50 >> 1毫摩尔）。研究发现，MAP4是mGluR4a的弱拮抗剂或部分激动剂（IC50 > 500微摩尔），且对30微摩尔（1S,3R）-ACPD对mGluR2的作用的拮抗作用较弱（IC50约为2毫摩尔）。
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