Estimation of D2-like receptor occupancy by dopamine in the putamen of hemiparkinsonian Monkeys.
Estimation of D2-like receptor occupancy by dopamine in the putamen of hemiparkinsonian Monkeys.
复制标题
半帕金森猴壳核中多巴胺对 D2 样受体占据的估计。
DOI：
10.1038/sj.npp.1301404
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Mukhin,AlexeyG
中科院分区：
文献类型：
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作者：
Chefer,SvetlanaI;Kimes,AlaneS;Matochik,JohnA;Horti,AndrewG;Kurian,Varughese;Shumway,Dean;Domino,EdwardF;London,EdytheD;Mukhin,AlexeyG
为了进一步了解帕金森氏病（PD）的神经化学变化，我们比较了多巴胺D2样多巴胺受体的占有率在控制和受损的壳核的四只猪尾猕猴单方面MPTP治疗。PET和体外结合技术分别用于测量结合电位（BP*）和D2样多巴胺受体密度（B max）。正如PD中所预期的，与每只动物的对侧壳核相比，在损伤中观察到相对较高的BP* 和B max值以及较少的安非他明诱导的[11 C]雷氯必利结合减少。无论测量的是[11 C]雷氯必利BP* 还是B max值，分别在体内和体外测量，损伤侧和对侧之间的百分比差异相似。由于[11 C]雷氯必利BP* 是可用于放射性配体结合的D2样多巴胺受体密度的量度（即，未被多巴胺占据），因此这些发现表明，受损壳核中内源性多巴胺对受体的占据分数几乎等于对侧壳核中的分数。因此，被多巴胺占据的受体的绝对数量，这是受体密度和多巴胺占据分数的乘积，在损伤中比在对侧壳核中更大。多巴胺对D2受体的部分占据率缺乏差异的一个可能的解释是（尽管可用的多巴胺损失）损伤诱导的一部分低亲和力D2受体增加到对多巴胺的高亲和力状态。
To advance understanding of the neurochemical changes in Parkinson's disease (PD), we compared D2-like dopamine receptor occupancy by dopamine in the control and lesioned putamen of four pig-tailed macaques treated unilaterally with MPTP. PET and in vitro binding techniques were used to measure binding potential (BP*) and density of D2-like dopamine receptors (B max), respectively. As would be expected in PD, relatively higher values of BP* and B max and less amphetamine-induced decrease in [11 C] raclopride binding were observed in the lesioned compared with the contralateral putamen in each animal. The percent differences between lesioned and contralateral sides were similar whether the measurements were of [11 C] raclopride BP* or B max values, measured in vivo and in vitro, respectively. As [11 C] raclopride BP* is a measure of the density of D2-like dopamine receptors available for radioligand binding (ie, not occupied by dopamine), these findings suggest that the fractional occupancy of receptors by endogenous dopamine in the lesioned putamen is nearly equal to that in the contralateral putamen. Therefore, the absolute number of receptors occupied by dopamine, which is a product of receptor density and fractional occupancy by dopamine, is greater in the lesioned than in the contralateral putamen. One possible explanation for the lack of differences in fractional occupancy of D2 receptors by dopamine (despite a loss in available dopamine) is a lesion-induced increase in a portion of low-affinity D2 receptors to a state of high affinity for dopamine.