AMG-1和腺苷对大鼠脑突触体谷氨酸释放的影响

观察了腺苷类化合物AMG-1对大鼠脑突触体前膜谷氨酸(glu)释放的影响。AMG-1在0.1～0.3 mmol·L^-1能明显抑制突触前膜Ca²⁺-依赖性glu的释放,并呈现剂量—效应关系。其作用强度与腺苷基本相似。提示AMG-1对脑保护作用可能与它激活腺苷A₁受体,从而抑制兴奋性氨基酸释放有关。

EFFECT OF AMG-1 AND ADENOSINE ON GLUTAMATE RELEASE FROM SYNAPTOSOMES IN RATS

The effects of AMG- 1 6 (5-hydroxy-2-methylpyridylamino)-9 ribofranosylpurine], an adenosine analogue, and adenosine on Ca²⁺-dependent and independent release of glutamate from rat synaptosomes induced by KC1 30 mmol · L^-1 were studied with an enzyme-linked fluorometric assay. The synaptosomes were prepared and preincubated for 30 min at 37℃. Two ml of incubation mixture containing synaptosomes(1.27 mg protein), NADP⁺ 1 mmol· L^-1, L-glutamic dehydrogenase 50 U, CaCl₂ 1.3 mmol ·L^-1 (or EGTA 1.3 mmol, L^-1) was transferred to the stirred cuvette in the fluorometer at 37℃ for 5 min. Then, AMG-1 (or adenosine) was added. Released glutamate (eg. fluorescent intensity) was monitored following the addition of 30 mmol · L^-1 KCl. The results indicate that Ca²⁺-dependent glutamate release from depolarized synaptosomes is inhibited by AMG-1 (0.1 mmol · L^-1) or adenosine ( 0.3 mmol · L^-1). The action of AMG-1 seems to be similar to that of adenosine. However, no change was found on Ca²⁺-independent release of glutamate. This implies that the protective effect of AMG-1 against cerebral ischemia may be partially due to inhibiting glutamate release from nerve terminal via the activation of adenosine A₁ receptor.