Wroblewska B, Wroblewski J T, Saab O H, Neale J H
Department of Biology, Georgetown University, Washington, D.C. 20057-1028.
J Neurochem. 1993 Sep;61(3):943-8. doi: 10.1111/j.1471-4159.1993.tb03606.x.
The neuronal dipeptide N-acetylaspartylglutamate (NAAG) fulfills several of the criteria for classification as a neurotransmitter including localization in synaptic vesicles, calcium-dependent release after neuronal depolarization, and low potency activation of N-methyl-D-aspartate receptors. In the present study, the influence of NAAG on metabotropic receptor activation in cerebellar granule cells was examined in cell culture. Stimulation of granule cell adenylate cyclase with forskolin increased cyclic AMP (cAMP) several hundredfold above basal levels within 10 min in a concentration-dependent manner. Although glutamate, NAAG, and the metabotropic receptor agonist trans-1-amino-1,3-cyclopentanedicarboxylic acid did not alter the low basal cAMP levels, the application of 300 microM glutamate or NAAG or trans-1-amino-1,3-cyclopentanedicarboxylic acid reduced forskolin-stimulated cAMP in granule cells by 30-50% in the absence or presence of inhibitors of ionotropic acidic amino acid receptors, as well as 2-amino-4-phosphonobutyrate. No additivity in the inhibition of cAMP was found when 300 microM NAAG and trans-1-amino-1,3-cyclopentanedicarboxylic acid were coapplied. The beta-analogue of NAAG failed to reduce cAMP levels. Similar effects of NAAG and glutamate were obtained under conditions of inhibition of phosphodiesterase activity and were prevented by pretreatment of the cells with pertussis toxin. These data are consistent with the activation by NAAG of a metabotropic acidic amino acid receptor coupled to an inhibitory G protein. In contrast, the metabotropic acidic amino acid receptor coupled to phosphoinositol turnover in these cells was not activated by NAAG.(ABSTRACT TRUNCATED AT 250 WORDS)
神经元二肽N - 乙酰天门冬氨酰谷氨酸（NAAG）符合多种被归类为神经递质的标准，包括定位于突触小泡、神经元去极化后钙依赖性释放以及对N - 甲基 - D - 天冬氨酸受体的低效激活。在本研究中，在细胞培养中检测了NAAG对小脑颗粒细胞代谢型受体激活的影响。用福斯高林刺激颗粒细胞腺苷酸环化酶，可使环磷酸腺苷（cAMP）在10分钟内以浓度依赖性方式比基础水平增加数百倍。虽然谷氨酸、NAAG和代谢型受体激动剂反式 - 1 - 氨基 - 1,3 - 环戊烷二羧酸不会改变低基础cAMP水平，但在不存在或存在离子型酸性氨基酸受体抑制剂以及2 - 氨基 - 4 - 膦酰丁酸的情况下，应用300微摩尔谷氨酸或NAAG或反式 - 1 - 氨基 - 1,3 - 环戊烷二羧酸可使颗粒细胞中福斯高林刺激的cAMP降低30 - 50%。当共同应用300微摩尔NAAG和反式 - 1 - 氨基 - 1,3 - 环戊烷二羧酸时，未发现对cAMP抑制的相加作用。NAAG的β类似物未能降低cAMP水平。在抑制磷酸二酯酶活性的条件下，NAAG和谷氨酸获得了类似的效果，并且用百日咳毒素预处理细胞可阻止这种效果。这些数据与NAAG激活与抑制性G蛋白偶联的代谢型酸性氨基酸受体一致。相比之下，这些细胞中与磷酸肌醇周转偶联的代谢型酸性氨基酸受体未被NAAG激活。（摘要截短于250字）
