Cunha R A, Constantino M C, Sebastião A M, Ribeiro J A
Lab. Pharmacology, Gulbenkian Institute of Science, Oeiras, Portugal.
Neuroreport. 1995 Jul 31;6(11):1583-8. doi: 10.1097/00001756-199507310-00029.
Age-related changes of A1 and A2a adenosine receptor binding characteristics were investigated in three regions of the rat brain using the A1 selective antagonist [3H]DPCPX, and the A2a selective agonist [3H]CGS 21680. The density of A1 binding sites in aged rats (24 months) was decreased by 33% in the hippocampus and by 60% in the cortex and was unchanged in the striatum when compared with young adult rats (6 weeks), with no change in KD. There were also age-related changes in the density of A2a binding sites: in the cortex, there was a 94% increase in the number of [3H]CGS 21680 binding sites in aged rats compared with young rats, and a similar tendency was observed in the hippocampus (32% increase in A2a binding sites in aged rats), with no change in KD; in the striatum there was a tendency for a decrease (22%) in the number of [3H]CGS 21680 binding sites in aged rats, and a decrease in KD. These results suggest that there are age-related changes in the balance between inhibitory A1- and excitatory A2a-adenosine receptor-mediated actions, which vary in different brain areas: in the cortex and hippocampus, the balance might be shifted towards adenosine-mediated excitatory actions, since there is an increase in the number of A2a receptors and a decrease in the number of A1 receptors upon ageing. In contrast, in the striatum, the A1/A2a ratio might be only slightly affected upon ageing.
使用A1选择性拮抗剂[3H]DPCPX和A2a选择性激动剂[3H]CGS 21680，研究了大鼠脑三个区域中与年龄相关的A1和A2a腺苷受体结合特性的变化。与年轻成年大鼠（6周龄）相比，老年大鼠（24月龄）海马中A1结合位点的密度降低了33%，皮质中降低了60%，纹状体中则无变化，KD也没有改变。A2a结合位点的密度也存在与年龄相关的变化：在皮质中，老年大鼠[3H]CGS 21680结合位点的数量比年轻大鼠增加了94%，海马中也观察到类似趋势（老年大鼠A2a结合位点增加32%），KD没有变化；在纹状体中，老年大鼠[3H]CGS 21680结合位点的数量有减少的趋势（22%），KD降低。这些结果表明，抑制性A1和兴奋性A2a腺苷受体介导的作用之间的平衡存在与年龄相关的变化，且在不同脑区有所不同：在皮质和海马中，随着年龄增长，A2a受体数量增加而A1受体数量减少，平衡可能向腺苷介导的兴奋性作用偏移。相比之下，在纹状体中，衰老对A1/A2a比值的影响可能较小。
