Lombardi G, Pellegrini-Giampietro D E, Leonard P, Cherici G, Pellicciari R, Moroni F
Dipartimento di Farmacologia Preclinica, Università di Firenze, Italy.
Neurochem Int. 1994 Jun;24(6):525-32. doi: 10.1016/0197-0186(94)90003-5.
Rat brain slices were used to study the effects of different metabotropic glutamate receptor ligands on (i) the depolarization (30 mM KCl)-induced outflow of previously taken up D-[3H]aspartate; (ii) the inhibition of forskolin (30 microM)-induced cyclic AMP accumulation; and (iii) the hydrolysis of phosphoinositides. In addition, the localization of mRNAs coding for different metabotropic glutamate receptor subtypes was detected using in situ hybridization. (1S-3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (30-300 microM), a non selective metabotropic glutamate receptor agonist, significantly increased the KCl-induced output of radioactivity from cortical slices, whereas it inhibited the output from striatal slices. Conversely, (1S,3S,4S)-carboxycyclopropylglycine (0.1-1 microM), a relatively selective agonist of the mGluR2 metabotropic glutamate receptor subtype, had an inhibitory effect on the output of D-[3H]aspartate from both cortical and striatal slices and proved to be the most potent metabotropic glutamate receptor agonist in inhibiting cyclic AMP accumulation, but not in stimulating phosphoinositide hydrolysis. Since 2-amino-4-phosphonobutyrate (a mGluR4, mGluR6 and mGluR7 agonist) was not active in any of the assays tested, we hypothesized that the mGluR2 subtype could be involved in these events. Accordingly, mGluR2 mRNA expression was abundant in cortical neurons projecting to the striatum. Our experiments suggest that the stimulation of metabotropic glutamate receptors may either decrease or increase transmitter release depending on the subtype that prevails in the region under study.
(i) 去极化（30 mM KCl）诱导的先前摄取的D-[3H]天冬氨酸外流；(ii) 福斯可林（30 μM）诱导的环磷酸腺苷积累的抑制；以及(iii) 磷酸肌醇的水解。此外，使用原位杂交检测编码不同代谢型谷氨酸受体亚型的mRNA的定位。(1S-3R)-1-氨基环戊烷-1,3-二羧酸（30 - 300 μM），一种非选择性代谢型谷氨酸受体激动剂，显著增加了皮质切片中KCl诱导的放射性输出，而抑制了纹状体切片中的输出。相反，(1S,3S,4S)-羧基环丙基甘氨酸（0.1 - 1 μM），一种mGluR2代谢型谷氨酸受体亚型的相对选择性激动剂，对皮质和纹状体切片中D-[3H]天冬氨酸的输出均有抑制作用，并且被证明是抑制环磷酸腺苷积累但不刺激磷酸肌醇水解的最有效代谢型谷氨酸受体激动剂。由于2-氨基-4-膦酰丁酸（一种mGluR4、mGluR6和mGluR7激动剂）在任何测试的实验中均无活性，我们推测mGluR2亚型可能参与这些事件。相应地，mGluR2 mRNA表达在投射到纹状体的皮质神经元中丰富。我们的实验表明，代谢型谷氨酸受体的刺激可能根据所研究区域中占主导的亚型而减少或增加神经递质释放。
