van der Werf J F, Sebens J B, Vaalburg W, Korf J
Eur J Pharmacol. 1983 Feb 18;87(2-3):259-70. doi: 10.1016/0014-2999(83)90336-9.
The accumulation and retention of radioactivity in rat brain were studied after intravenous injection of the dopamine (DA) agonist [3H]N-n-propylnorapomorphine ( [3H]NPA). Dose-dependent saturable accumulation of label was found in the striatum, nucleus accumbens and olfactory tubercle. DA agonists (apomorphine, N,N-dipropyl-5,6-ADTN) and antagonists (haloperidol, cis-flupenthixol) prevented this accumulation. Enhanced accumulation of radioactivity in the striatum was found after 6-OHDA lesions and short- and long-term treatment with reserpine. These results are an indication of specific NPA binding to presumably postsynaptically situated DA receptors. One hour after administration of the drug, the effect of NPA on striatal DA metabolism was not correlated with receptor saturation. Maximal numbers of in vivo NPA binding sites (about 30 and 22 pmol . g-1) in striatal tissue were calculated from independent measurements at 15 and 60 min after NPA injection. Regional distribution of radioactivity after a tracer dose of [3H]NPA was assessed in 35 brain areas and parts of the spinal cord. In addition to the already mentioned DA-rich areas receptor-specific NPA binding was also found in several other brain parts.
静脉注射多巴胺(DA)激动剂[3H]N-正丙基去甲阿朴吗啡([3H]NPA)后,研究了其在大鼠脑内的放射性积累和滞留情况。在纹状体、伏隔核和嗅结节中发现了放射性标记的剂量依赖性饱和积累。DA激动剂(阿朴吗啡、N,N-二丙基-5,6-ADTN)和拮抗剂(氟哌啶醇、顺式氟奋乃静)可阻止这种积累。6-羟基多巴胺损伤以及利血平短期和长期治疗后,纹状体中放射性的积累增强。这些结果表明NPA与可能位于突触后的DA受体特异性结合。给药1小时后,NPA对纹状体DA代谢的影响与受体饱和无关。根据NPA注射后15分钟和60分钟的独立测量结果,计算出纹状体组织中体内NPA结合位点的最大数量(约30和22 pmol·g-1)。在35个脑区和部分脊髓中评估了示踪剂量的[3H]NPA后的放射性区域分布。除了上述富含DA的区域外,在其他几个脑区也发现了受体特异性NPA结合。