Saugstad J A, Segerson T P, Westbrook G L
Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
Eur J Pharmacol. 1995 Apr 28;289(2):395-7. doi: 10.1016/0922-4106(95)90120-5.
The aspartate analog 2-amino-3-phosphonopropionic acid (AP3) antagonizes glutamate-stimulated phosphatidyl inositide hydrolysis in brain slices, but is reportedly weak or ineffective in antagonizing the phosphatidyl inositide-coupled cloned metabotropic glutamate receptors 1 alpha and 5. Thus we examined the pharmacological properties of AP3 on mGlu1 alpha and mGlu5 receptor responses in Xenopus oocytes. DL-AP3 antagonized mGlu1 alpha and mGlu5 responses, but antagonism was overcome at high glutamate concentrations consistent with competitive inhibition (IC50 = 2.1 mM for mGlu1 alpha). Both responses were also inhibited by (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG). We conclude that the available antagonists cannot distinguish between the mGlu1 alpha receptor and mGlu5 receptor, and that antagonism by AP3 may be obscured in the presence of high agonist concentrations or in cells with spare receptors.
天冬氨酸类似物2-氨基-3-膦酰丙酸（AP3）可拮抗脑片中谷氨酸刺激的磷脂酰肌醇水解，但据报道，它在拮抗与磷脂酰肌醇偶联的克隆代谢型谷氨酸受体1α和5方面作用较弱或无效。因此，我们研究了AP3对非洲爪蟾卵母细胞中mGlu1α和mGlu5受体反应的药理学特性。DL-AP3可拮抗mGlu1α和mGlu5反应，但在高谷氨酸浓度下拮抗作用被克服，这与竞争性抑制一致（mGlu1α的IC50 = 2.1 mM）。（RS）-α-甲基-4-羧基苯基甘氨酸（MCPG）也可抑制这两种反应。我们得出结论，现有的拮抗剂无法区分mGlu1α受体和mGlu5受体，并且在高激动剂浓度存在或在具有备用受体的细胞中，AP3的拮抗作用可能会被掩盖。
