[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 KCl 30 mmol.L-1 were studied with an enzyme-linked fluorometric assay. The synaptosomes were prepared and preincubated for 30 min at 37 degrees C. 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 degrees C 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.
Department of Pharmacology, Chinese Academy of Medical Sciences, Beijing.
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Liu
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Feng
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D005971:Glutamates / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000378:metabolism*
D005971:Glutamates; C063248:6-(5-hydroxy-2-pyridylmethylamino)-9-beta-ribofuranosylpurine; D000241:Adenosine