Protection against kainate-induced excitotoxicity by adenosine A_2A receptor agonists and antagonists

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• 作者：Jones ; P. A. ; Smith ; R. A. ; Stone ; T. W.
• 关键词：kainate ; excitotoxicity ; purines ; CGS21680 ; ZM241385 ; adenosine ; APEC ; 2-[(2-aminoethylamino)-carbonylethylphenylethyl amino]-5&prime ; -N-ethylcarboxamidoadenosine ; CGS21680 ; 2-p-(2-carboxyethyl)phenethylamino-5&prime ; -N-ethylcarboxamidoadenosine hydrochlo
• 刊名：Neuroscience
• 出版年：1998
• 出版时间：July, 1998
• 年：1998
• 卷：85
• 期：1
• 页码：229-237
• 全文大小：836 K

文摘

The neuroprotective role of adenosine receptor agonists in various models of ischaemia and neuronal excitotoxicity has been attributed to adenosine A₁ receptor activation. In this study we examine the role of the A_2A receptor in the kainate model of excitotoxicity. Kainate (10 mg/kg) was administered systemically 10 min after the intraperitoneal injection of adenosine analogues. The A_2A agonist 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride (CGS21680) protected the hippocampus at concentrations of 0.1 and 0.01 mg/kg, but not at 2 56;g/kg. The addition of the centrally acting adenosine A₁ receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine partially reduced protection only in the CA3a region, suggesting that only a small proportion of the protection was attributable to the A₁ receptor. A less potent A_2A agonist, N⁶-[2-(3,5-dimethyoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (1 mg/kg), provided only partial protection against kainate. 4-(2-[7-Amino-2-[2-furyl][1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol, a selective A_2A antagonist, also showed protection against kainate-induced neuronal death, when administered alone or in combination with CGS21680.