Pang C S, Tang P L, Song Y, Pang S F, Ng K W, Guardiola-Lemaitre B, Delagrange P, Brown G M
The Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
J Pineal Res. 1997 Oct;23(3):148-55. doi: 10.1111/j.1600-079x.1997.tb00348.x.
We have compared the 50% inhibition values of 2-[125I]iodomelatonin ([125I]Mel) competition curves by melatonin and 3 naphthalenic ligands, N-[2-(7-methoxy-1-naphthyl) ethyl] cyclobutane carboxamide (S20642), N-propyl N-[2-(7-methoxy-1-naphtyl) ethyl] urea (S20753), and N-[2-(7-methoxy-1-naphthyl) ethyl] crotonamide (S20750), using membrane preparations of four tissues (lung, spleen, brain, and kidney) of the chicken simultaneously. In retired breeders, we have demonstrated that the affinities of S20642 were similar in the lung and spleen. However they were 2-fold lower in the brain and 80-fold lower in the kidney. Similar differential binding affinities to the melatonin receptors were observed in the four tissues of young male chicks. This suggests that age and sex have little influence on the differential inhibitory properties of melatonin and S20642 in the tissues studied. The addition of guanosine 5'-O-thiotriphosphate (GTPgammaS), which encouraged the uncoupling of melatonin receptor to the G protein complex, lowered the binding affinity of melatonin and S20642 in the tissues studied but their differential affinities in the four tissues were however maintained. The affinities of 5-methoxy-N-cyclopropanoyltryptamine (CPMT) in the kidney were also 5-10-fold lower than those in the lung, spleen, and brain of young male chicks. The distinctive differential affinities of melatonin, S20642, and CPMT for [125I]Mel binding sites in the chicken lung, spleen, brain, and kidney indicated that the binding sites in these tissues are heterogeneous. Our study implicated that the naphthalenic ligand S20642 may be a useful melatonin analog to distinguish melatonin receptor subtypes in tissues and a possible drug candidate worthwhile for further investigations.
我们同时使用鸡的四种组织（肺、脾、脑和肾）的膜制剂，比较了褪黑素和3种萘基配体N-[2-(7-甲氧基-1-萘基)乙基]环丁烷甲酰胺（S20642）、N-丙基-N-[2-(7-甲氧基-1-萘基)乙基]脲（S20753）以及N-[2-(7-甲氧基-1-萘基)乙基]巴豆酰胺（S20750）对2-[125I]碘褪黑素（[125I]Mel）竞争曲线的50%抑制值。在老龄种鸡中，我们已证明S20642在肺和脾中的亲和力相似。然而，其在脑中的亲和力低2倍，在肾中低80倍。在年轻雄性雏鸡的四种组织中也观察到了对褪黑素受体类似的差异结合亲和力。这表明年龄和性别对所研究组织中褪黑素和S20642的差异抑制特性影响很小。添加鸟苷5'-O-硫代三磷酸（GTPγS）可促使褪黑素受体与G蛋白复合物解偶联，降低了所研究组织中褪黑素和S20642的结合亲和力，但它们在四种组织中的差异亲和力得以维持。5-甲氧基-N-环丙酰色胺（CPMT）在年轻雄性雏鸡肾中的亲和力也比在肺、脾和脑中低5至10倍。褪黑素、S20642和CPMT对鸡肺、脾、脑和肾中[I]Mel结合位点的独特差异亲和力表明，这些组织中的结合位点是异质的。我们的研究表明，萘基配体S20642可能是一种用于区分组织中褪黑素受体亚型的有用褪黑素类似物，也是一个值得进一步研究的潜在药物候选物。
