Burnett D M, Zahniser N R
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Synapse. 1989;4(2):143-55. doi: 10.1002/syn.890040208.
The effects of aging on the density and affinity of alpha 1-adrenergic receptors (alpha 1-ARs) were studied in several circumscribed areas of the Fischer 344 male rat brain. Computer-assisted quantitative autoradiography was used to analyze saturation binding isotherms of [125I]BE-2254, a selective alpha 1-AR antagonist. Significant decreases in receptor density of 15 and 29% were observed in the thalamus at 16-18 and 24-28 months of age, respectively, when compared to 3-4-month-old controls. Progressive declines in receptor density of 24 and 44% were also found in the olfactory tubercle. In the cerebral cortex, a significant 26% loss in receptors occurred only in the oldest age group. No changes were found in any of the other brain areas investigated, including the cerebellum, brainstem, caudate-putamen, and several subregional areas of the hippocampal formation. Kd values ranged from 12 +/- 1.8 pM in the brainstem to 23 +/- 1.6 pM in the thalamus and were not affected by aging in any area examined. It is concluded that the density of alpha 1-ARs in the Fischer 344 rat brain is diminished with aging in a region-specific manner and that loss of these receptors may account for age-related functional deficits only in a few brain areas.
在雄性Fischer 344大鼠脑的几个限定区域研究了衰老对α1-肾上腺素能受体(α1-ARs)密度和亲和力的影响。使用计算机辅助定量放射自显影术分析选择性α1-AR拮抗剂[125I]BE-2254的饱和结合等温线。与3-4月龄对照组相比,16-18月龄和24-28月龄大鼠丘脑的受体密度分别显著降低了15%和29%。嗅结节的受体密度也逐渐下降,分别降低了24%和44%。在大脑皮层,仅在最老的年龄组中受体显著减少了26%。在其他任何研究的脑区,包括小脑、脑干、尾状核-壳核和海马结构的几个亚区域,均未发现变化。解离常数(Kd)值范围从脑干的12±1.8 pM到丘脑的23±1.6 pM,在所检查的任何区域均不受衰老影响。结论是,Fischer 344大鼠脑中α1-ARs的密度随衰老呈区域特异性降低,这些受体的丧失可能仅在少数脑区导致与年龄相关的功能缺陷。