Distinct binding patterns of [H-3]raclopride and [H-3]spiperone at dopamine D-2 receptors in vivo in rat brain. Implications for PET studies.
Distinct binding patterns of [H-3]raclopride and [H-3]spiperone at dopamine D-2 receptors in vivo in rat brain. Implications for PET studies.
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DOI：
10.3109/10799899709036618
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发表时间：
1997-01-01
期刊：
影响因子：
--
通讯作者：
Gunst, F
中科院分区：
文献类型：
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作者：
Bischoff, S;Gunst, F
对精神分裂症患者多巴胺（DA）D-2受体的正电子发射断层扫描（PET）研究提供了相互矛盾的数据，这可能是因为通常使用的配体雷氯必利（RAG）和螺哌隆（SPI）没有标记相同的位点。在这项研究中，我们发现[H-3]RAC和[H-3]SPI在大鼠脑中的体内结合特性在许多方面不同。1)[H-3]RAC在纹状体和嗅结节中标记的位点是其两倍，[H-3]SPI在垂体中标记的位点是其两倍。2)在纹状体中，[H-3]RAC的动力学比[H-3]SPI短得多。3)与SPI不同，RAG没有表现出边缘选择性。4)内源性DA对[H-3]RAC和[H-3]SPI结合的调节是完全相反的：D-苯丙胺降低，利血平+ α-甲基-p-酪氨酸增加纹状体中[H-3]RAC结合，而[H-3]SPI则相反。[H-3]RAC和[H-3]SPI的这种不同结合模式表明这两种放射性配体不标记相同的受体位点。
Positron emission tomography studies (PET) on dopamine (DA) D-2 receptors of schizophrenics provided conflicting data, perhaps because the ligands generally used, raclopride (RAG) and spiperone (SPI), did not label the same sites. In this study, we found that the in vivo binding characteristics of [H-3]RAC and of [H-3]SPI in rat brain, differed in many ways. 1) [H-3]RAC labeled twice as many sites in striatum and olfactory tubercle and [H-3]SPI twice as many sites in pituitary. 2) The kinetic was much shorter with [H-3]RAC than [H-3]SPI in striatum. 3) RAG, unlike SPI, did not exhibit limbic selectivity. 4) The modulation of [H-3]RAC and [H-3]SPI binding by endogenous DA were diametrically opposite: D-amphetamine decreased, and reserpine + alpha-methyl-p-tyrosine increased [H-3]RAC binding in striatum whereas the opposite occured with [H-3]SPI. This distinct binding pattern of [H-3]RAC and [H-3]SPI suggests that these two radioligands do not label the same receptor sites.