Jones N M, Lawrence A J, Beart P M
Department of Pharmacology, Monash University, Clayton, Vic., Australia.
Neurochem Int. 1998 Jan;32(1):31-8. doi: 10.1016/s0197-0186(97)00050-8.
The functional involvement of metabotropic glutamate receptors in nucleus tractus solitarius of the medulla has been examined by evaluating the action of the selective metabotropic glutamate receptor agonist trans-1-amino-cyclopentane-1,3-dicarboxylate on the extracellular release of L-glutamate and L-aspartate by in vivo microdialysis. Studies were performed in urethane anaesthetized rats, with a microdialysis probe being inserted into the medial nucleus tractus solitarius, which was constantly perfused with artificial cerebrospinal fluid (1 microliter/min). Following an equilibration period, samples were collected for amino acid analysis by HPLC. trans-1-Amino-cyclopentane-1,3-dicarboxylate (30 microM) produced 190% and 500% increases in basal release of L-glutamate and L-aspartate, respectively. trans-1-Amino-cyclopentane-1,3-dicarboxylate-evoked release of L-glutamate and L-aspartate was concentration-dependent (10-100 microM), and was calcium and tetrodotoxin-sensitive. Two metabotropic glutamate receptor antagonists, (+)-alpha-methyl-4-carboxyphenylglycine (200 microM) and (S)-4-carboxyphenylglycine (500 microM), when administered via a microdialysis probe, significantly attenuated the trans-1-amino-cyclopentane-1,3-dicarboxylate-evoked release of both L-glutamate and L-aspartate. Basal release was not altered by these two antagonists. Histological studies verified the location of the probe in the nucleus tractus solitarius. These studies provide the first evidence using in vivo microdialysis of functional metabotropic glutamate receptors, which seem to be facilitatory pre- and postsynaptically located receptors, in the rat nucleus tractus solitarius. On the basis of our findings, metabotropic glutamate receptors are likely to play key modulatory roles in regulating transmitter release.
通过体内微透析评估选择性代谢型谷氨酸受体激动剂反式-1-氨基环戊烷-1,3-二羧酸对L-谷氨酸和L-天冬氨酸细胞外释放的作用，研究了延髓孤束核中代谢型谷氨酸受体的功能参与情况。实验在氨基甲酸乙酯麻醉的大鼠中进行，将微透析探针插入内侧孤束核，并用人工脑脊液（1微升/分钟）持续灌注。平衡期后，收集样本通过高效液相色谱法进行氨基酸分析。反式-1-氨基环戊烷-1,3-二羧酸（30微摩尔）使L-谷氨酸和L-天冬氨酸的基础释放分别增加了190%和500%。反式-1-氨基环戊烷-1,3-二羧酸诱发的L-谷氨酸和L-天冬氨酸释放呈浓度依赖性（10 - 100微摩尔），且对钙和河豚毒素敏感。两种代谢型谷氨酸受体拮抗剂，（+）-α-甲基-4-羧基苯甘氨酸（200微摩尔）和（S）-4-羧基苯甘氨酸（500微摩尔），通过微透析探针给药时，显著减弱了反式-1-氨基环戊烷-1,3-二羧酸诱发的L-谷氨酸和L-天冬氨酸释放。这两种拮抗剂未改变基础释放。组织学研究证实了探针在孤束核中的位置。这些研究首次提供了在大鼠孤束核中使用体内微透析对功能性代谢型谷氨酸受体的证据，这些受体似乎是突触前和突触后起促进作用的受体。根据我们的研究结果，代谢型谷氨酸受体可能在调节递质释放中起关键的调节作用。
