Leff S E, Gariano R, Creese I
Proc Natl Acad Sci U S A. 1984 Jun;81(12):3910-4. doi: 10.1073/pnas.81.12.3910.
The time course of recovery of [3H]spiperone binding in the rat striatum after a single injection of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) shows that a slower rate of regeneration/turnover of D-2 dopamine receptors occurs in mid-life-mature versus young male rats. This slower receptor recovery reflects relatively slower rates of both receptor synthesis and degradation. Studies using cycloheximide indicate that protein synthesis plays a significant role in the reappearance of [3H]spiperone-binding sites. Other experiments indicate that chronic reserpine treatment, which produces dopamine receptor up regulation, also produces accelerated receptor recovery after EEDQ blockade. An age-related decline in dopamine receptor turnover, if present in humans and progressive into senescence, could be responsible for the increased risk of developing Parkinson disease and drug-induced parkinsonian-like extrapyramidal side effects with age. On the other hand, the more rapid receptor turnover rates seen in young rats may be a biochemical feature related to plasticity in the striatum during development.
单次注射不可逆拮抗剂N-乙氧羰基-2-乙氧基-1,2-二氢喹啉（EEDQ）后，大鼠纹状体中[3H]司哌罗宁结合的恢复时间进程表明，中年成熟雄性大鼠与年轻雄性大鼠相比，D-2多巴胺受体的再生/周转速率较慢。这种较慢的受体恢复反映了受体合成和降解速率相对较慢。使用环己酰亚胺的研究表明，蛋白质合成在[3H]司哌罗宁结合位点的重新出现中起重要作用。其他实验表明，长期利血平治疗可导致多巴胺受体上调，在EEDQ阻断后也会使受体恢复加速。如果人类存在与年龄相关的多巴胺受体周转下降并持续到衰老，可能是导致帕金森病风险增加以及随着年龄增长药物诱发帕金森样锥体外系副作用的原因。另一方面，年轻大鼠中观察到的较快受体周转速率可能是与纹状体发育过程中的可塑性相关的生化特征。
