Long-term effect of convulsive behavior on the density of adenosine A1 and A2A receptors in the rat cerebral cortex
Long-term effect of convulsive behavior on the density of adenosine A1 and A2A receptors in the rat cerebral cortex
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DOI：
10.1111/j.1528-1167.2005.01026.x
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发表时间：
2005-01-01
期刊：
影响因子：
5.6
通讯作者：
Cunha, RA
中科院分区：
文献类型：
--
作者：
Rebola, N;Porciúncula, LV;Cunha, RA
目的：腺苷是一种神经调节剂，主要通过抑制A受体发挥抗惊厥作用，但最近的数据表明易化性A(2A)受体的基因缺失也可能减轻惊厥。由于A(1)和A(2A)受体在不同的应激状态下都容易下调和上调，我们研究了惊厥行为是否会导致大脑皮层A(1)和A(2A)受体密度的长期变化。方法：成年Wistar大鼠通过刺激杏仁核(点燃)或腹腔注射海人藻酸(10 mg/ml)诱导4-5级惊厥(racine‘s Scale)。结果：A(1)拮抗剂H-3-DPCPX的结合密度降低了40%。+/-4.4%，点燃或注射海人酸后20.7+/-0.5%。同样，点燃或注射红藻氨酸大鼠大脑皮层A受体免疫反应性分别下降19.1%、3.3%和12.7%、5.7%。而点燃或海人藻酸注射大鼠皮质膜上A(2A)受体拮抗剂3H-SCH-58261的结合密度分别增加29334%和15932%，A(2A)受体免疫反应性也增加15112%和79.6 7.0%。结论：惊厥后A受体长期减少，A(2A)受体密度增加，提示A(2A)受体拮抗剂可能比A(1)激动剂更有应用前景。
Purpose: Adenosine is a neuromodulator that has been proposed to act as an anticonvulsant mainly via inhibitory A, receptors, but recent data show that genetic deletion of facilitatory A(2A) receptors might also attenuate convulsions. Since both A(1) and A(2A), receptors are prone to down- and upregulation in different stressful situations, we investigated if convulsive behavior leads to a long-term change in A(1) and A(2A) receptor density in the rat cerebral cortex.Methods: Stage 4-5 convulsions (Racine's scale) were induced in adult Wistar rats either through amygdala stimulation (kindling) or by intraperitoneal injection of kainate (10 mg/ml). Rats were killed after 4 weeks to evaluate adenosine A(1) and A(2A) receptor density in the cerebral cortex using both Western blot and membrane binding assays.Results: The binding density of the A(1) antagonist, H-3-DPCPX, decreased by 40. +/- 4.4% and by 20.7 +/- 0.5% after kindling or kainate injection. Likewise, A, receptor immunoreactivity in cortical membranes from kindled or kainate-injected rats decreased by 19.1 3.3% and 12.7 5.7%, respectively. In contrast, the binding density of the A(2A) receptor antagonist 3 H-SCH 58261 increased by 293 34% and by 159 32% in cortical membranes from kindled or kainate-injected rats, and A(2A) receptor immunoreactivity also increased by 151 12% and 79.6 7.0%.Conclusions: This indicates that after convulsive behavior there is a long-term decrease of A, receptors accompanied by an increased density of A(2A) receptors, suggesting that A(2A) antagonists rather than A(1) agonists may be more promising anticonvulsive drugs.