Davies B, Hannah L T, Randall C F, Bromage N, Williams L M
Institute of Aquaculture, University of Stirling, Scotland.
Gen Comp Endocrinol. 1994 Oct;96(1):19-26. doi: 10.1006/gcen.1994.1155.
A combination of in vitro autoradiography and membrane homogenate receptor assays has been used to localize and characterized 2-[125I]iodomelatonin binding sites in the brain of the rainbow trout (Onchorhynchus mykiss). Specific 2-[125I]iodomelatonin binding, defined as that displaced by 1 microM melatonin, increased linearly with increasing protein concentration in membrane homogenates of whole trout brain. Specific binding was both time and temperature dependent and reversible in the presence of 1 microM melatonin. Binding was saturable at between 100-150 pM 2-[125I]iodomelatonin and Scatchard analysis of saturation isotherms revealed a dissociation constant (Kd) of 15.00 +/- 0.95 pM and a maximum receptor number (Bmax) of 42.35 +/- 2.70 fm/mg protein (n = 16). Addition of 10(-4) M GTP gamma S (an analogue of guanosine triphosphate) to saturation isotherms apparently reduced the Bmax by 75% on average with no apparent change in the affinity of the binding. Scatchard analysis of saturation isotherms generated from whole brain membrane homogenates of trout kept on long days (15 hr light:9 hr dark) and killed either during the midlight or middark phase showed no significant differences in either the Kd or the Bmax of 2-[125I]iodomelatonin binding, although a robust rhythm in melatonin concentration was confirmed in these fish. Displacement of 2-[125I]iodomelatonin binding with increasing concentrations of competing ligands gave an order of potency of 2-iodomelatonin > melatonin >> 5-HT. Localization of specific central 2-[125I]iodomelatonin binding in the rainbow trout showed high levels of binding associated with neuronal areas involved in the processing of visual signals, particularly the optic tectum and nucleus rotundus.(ABSTRACT TRUNCATED AT 250 WORDS)
采用体外放射自显影和膜匀浆受体分析相结合的方法,对虹鳟(Onchorhynchus mykiss)脑中2-[125I]碘褪黑素结合位点进行了定位和特性研究。特异性2-[125I]碘褪黑素结合(定义为被1 microM褪黑素取代的结合)在整个鳟鱼脑的膜匀浆中随蛋白质浓度增加呈线性增加。特异性结合具有时间和温度依赖性,在1 microM褪黑素存在下是可逆的。在100 - 150 pM 2-[125I]碘褪黑素之间结合达到饱和,对饱和等温线的Scatchard分析显示解离常数(Kd)为15.00±0.95 pM,最大受体数(Bmax)为42.35±2.70 fm/mg蛋白质(n = 16)。向饱和等温线中加入10(-4) M GTPγS(鸟苷三磷酸类似物),平均使Bmax降低75%,结合亲和力无明显变化。对处于长日照(15小时光照:9小时黑暗)且在光照中期或黑暗中期处死的鳟鱼全脑膜匀浆产生的饱和等温线进行Scatchard分析,结果显示2-[125I]碘褪黑素结合的Kd或Bmax均无显著差异,尽管这些鱼体内褪黑素浓度呈现明显的节律性。用浓度递增的竞争配体取代2-[125I]碘褪黑素结合,其效力顺序为2-碘褪黑素>褪黑素>>5-羟色胺。虹鳟脑中特异性中枢2-[125I]碘褪黑素结合的定位显示,高水平结合与参与视觉信号处理的神经元区域相关,特别是视顶盖和圆核。(摘要截短于250字)