Astrocytic gamma-aminobutyric acid (GABA) transporters mediate guanidinoacetate transport in rat brain

作者：Tachikawa Masanori^*; Yashiki Ayane; Akanuma Shin ichi; Matsukawa Haruka; Ide Soichiro; Minami Masabumi; Hosoya Ken ichi^*

来源：Neurochemistry International, 2018, 113: 1-7.

DOI：10.1016/j.neuint.2017.11.013

• Guanidinoacetate
• Creatine
• GABA transporter
• Astrocyte
• GABA
• Neuron-glial relationship

Guanidinoacetate (GM) is a biosynthetic precursor of creatine, which plays a critical role in homeostasis of high-energy phosphates in the brain, but cerebral accumulation of GM leads to neurological complications, such as epilepsy and seizures. The purpose of the present study was to clarify the contribution of the gamma-aminobutyric acid (GABA) transport systems to GM transport in astrocytes by means of uptake studies in rat brain slices, primary astrocyte cultures and Chinese hamster ovary (CHO) cells expressing human GABA transporters (GATs). GAA uptake by rat brain slices was Na+- and Cl--dependent, and GABA-sensitive. The inhibitory effect of GABA, a common substrate of GATs, on GM uptake by the brain slices was similar to that of beta-alanine, a selective substrate of GAT2/Slc6a13, GAT3/Slc6a11, and taurine transporter (TauT)/Slc6a6. Taurine, a high-affinity substrate of TauT/Slc6a6, exhibited a lesser inhibitory effect. In contrast, betaine, a substrate of betaine-GABA transporter 1 (BGT1)/Slc6a12, and creatine, a substrate of creatine transporter (CRT)/Slc6a8, had little inhibitory effect. A similar inhibition profile was observed in primary-cultured astrocytes. CHO cells expressing human GAT2/SLC6A13, GAT3/SLC6A11 and BGT1/SLC6Al2 exhibited GM transport, whereas CHO cells expressing GAT1/SLC6A1 did not. The Michaelis-Menten values in CHO cells expressing GAT2/SLC6A13 and GAT3/SLC6A11 were similar to those in primary-cultured astrocytes. Overall, our results suggest that astrocytic GAT2/Slc6a13 and GAT3/Slc6a11 play major roles in GM uptake as regulatory mechanisms of GM in rat brain, while TauT/Slc6a6, BGT1/Slc6a12, and CRT/Slc6a8 make relatively small contributions.

• 出版日期2018-2
• 单位河北医科大学