Okada M, Kawata Y, Murakami T, Wada K, Mizuno K, Kaneko S
Department of Neuropsychiatry, Hirosaki University, Japan.
Neuropharmacology. 1999 May;38(5):707-15. doi: 10.1016/s0028-3908(98)00226-3.
The effects of purinoceptor subtypes on hippocampal extracellular serotonin levels were determined by using in vivo microdialysis. Perfusion with adenosine-5'-triphosphate (ATP) for 20 min produced concentration-dependent changes in hippocampal extracellular serotonin levels, which consisted of an initial rise phase, with levels increasing to 309% of control with 100 microM ATP, followed by a later rebound reduction phase, with levels decreasing to 6% of control. The P2X1-7 active P2 purinoceptor agonist, 2-methylthioATP (2-MeSATP: 100 microM) increased the extracellular serotonin level drastically (638%), while the P2X1,3 active P2 purinoceptor agonist, alpha, beta-methylene-L-ATP (alpha, beta-meATP: 100 microM) produced a small increase (132%) in the serotonin level. The P2X1,2,3,5,7 active P2 purinoceptor antagonist, suramin (100 microM), reduced the basal serotonin level (86%) and the ATP-evoked initial rise phase (from 309 to 254%) without affecting the late reduction phase. The adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT: 50 microM) potentiated the rising phase (167%) and abolished the subsequent ATP-evoked reduction phase. Perfusion with CPT and an adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX: 10 microM), reduced the ATP-evoked initial rise (to 181%) and abolished the late reduction phases of serotonin release. These results indicate that ATP-evoked hippocampal serotonin release is composed of an initial rise phase and a later reduction phase. The ATP-evoked initial rise phase might be produced by an activation of P2X purinoceptor function, whereas the late reduction phase was modulated by the activation of adenosine A1 receptor function by adenosine, metabolized from ATP in the synaptic cleft.
通过体内微透析法测定嘌呤受体亚型对海马细胞外5-羟色胺水平的影响。用5'-三磷酸腺苷（ATP）灌注20分钟可使海马细胞外5-羟色胺水平产生浓度依赖性变化，包括一个初始上升阶段，100微摩尔ATP时水平升至对照的309%，随后是一个后期反弹降低阶段，水平降至对照的6%。P2X1-7活性P2嘌呤受体激动剂2-甲硫基ATP（2-MeSATP：100微摩尔）可使细胞外5-羟色胺水平急剧升高（638%），而P2X1,3活性P2嘌呤受体激动剂α,β-亚甲基-L-ATP（α,β-meATP：100微摩尔）可使5-羟色胺水平有小幅升高（132%）。P2X1,2,3,5,7活性P2嘌呤受体拮抗剂苏拉明（100微摩尔）可降低基础5-羟色胺水平（86%）以及ATP诱发的初始上升阶段（从309%降至254%），而不影响后期降低阶段。腺苷A1受体拮抗剂8-环戊基-1,3-二甲基黄嘌呤（CPT：50微摩尔）可增强上升阶段（167%）并消除随后ATP诱发的降低阶段。用CPT和腺苷A2受体拮抗剂3,7-二甲基-1-丙炔基黄嘌呤（DMPX：10微摩尔）灌注可降低ATP诱发的初始上升（至181%）并消除5-羟色胺释放的后期降低阶段。这些结果表明，ATP诱发的海马5-羟色胺释放由一个初始上升阶段和一个后期降低阶段组成。ATP诱发的初始上升阶段可能是由P2X嘌呤受体功能的激活产生的，而后期降低阶段则由突触间隙中由ATP代谢产生的腺苷激活腺苷A1受体功能所调节。
