Duarte João M N, Oliveira Catarina R, Ambrósio António F, Cunha Rodrigo A
Center for Neuroscience of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
Neurochem Int. 2006 Jan;48(2):144-50. doi: 10.1016/j.neuint.2005.08.008. Epub 2005 Oct 26.
Adenosine A(1) and A(2A) receptors are neuromodulatory systems that can control mnemonic behavior, which is modified by diabetes. Since the density of these adenosine receptors can change upon chronic noxious brain conditions, we now tested if the density of A(1) and A(2A) receptors was modified in the hippocampus of streptozotocin-induced diabetic rats. The binding density of the selective A(1) receptor antagonist, (3)H-DPCPX, was decreased by 36% in total hippocampal membranes 7 days after induction of diabetes and this down-regulation was maintained after 30 and 90 days, which was also confirmed by Western blot analysis of A(1) receptor immunoreactivity. In contrast, the binding density of the selective A(2A) receptor antagonist, (3)H-SCH 58261, was enhanced by 83% in total hippocampal membranes 7 days after induction of diabetes and this up-regulation persisted after 30 and 90 days. These results show that the balance between inhibitory A(1) and facilitatory A(2A) adenosine receptors is modified in the hippocampus of streptozotocin-induced diabetic rats. Thus, the most abundant A(1) receptors are down-regulated and there is an up-regulation of A(2A) receptors, suggesting a gain of function of hippocampal A(2A) receptors compared to A(1) receptors in diabetes, as has been observed in other chronic noxious brain conditions where A(2A) receptor blockade affords robust neuroprotection.
腺苷A(1)和A(2A)受体是神经调节系统，可控制受糖尿病影响而改变的记忆行为。由于这些腺苷受体的密度在慢性有害脑条件下会发生变化，我们现在测试了链脲佐菌素诱导的糖尿病大鼠海马中A(1)和A(2A)受体的密度是否发生改变。糖尿病诱导7天后，海马总膜中选择性A(1)受体拮抗剂(3)H-DPCPX的结合密度降低了36%，30天和90天后这种下调仍持续存在，这也通过A(1)受体免疫反应性的蛋白质印迹分析得到证实。相反，糖尿病诱导7天后，海马总膜中选择性A(2A)受体拮抗剂(3)H-SCH 58261的结合密度增加了83%，30天和90天后这种上调持续存在。这些结果表明，链脲佐菌素诱导的糖尿病大鼠海马中抑制性A(1)和促进性A(2A)腺苷受体之间的平衡发生了改变。因此，最丰富的A(1)受体下调，A(2A)受体上调，这表明与糖尿病中的A(1)受体相比，海马A(2A)受体的功能增强，正如在其他慢性有害脑条件下观察到的那样，其中A(2A)受体阻断可提供强大的神经保护作用。
