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首页> 外文期刊>Life sciences >Characterization of high-affinity (3H)TBZOH binding to the human platelet vesicular monoamine transporter.
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Characterization of high-affinity (3H)TBZOH binding to the human platelet vesicular monoamine transporter.

机译：高亲和力（3H）TBZOH结合人血小板水泡单胺转运蛋白的表征。

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The present study indicates that human platelets can be used as an accessible peripheral model not only for the plasma membrane serotonin transporter, but also for the vesicular monoamine transporter. The vesicular monoamine transporter (VMAT2) is responsible for the accumulation of monoamines in the synaptic vesicles. VMAT2 differs from the plasma membrane transporters in its capability to recognize serotonin, histamine, norepinephrine and dopamine with almost the same affinity. Dihydrotetrabenazine (TBZOH) is a very potent inhibitor of VMAT2 that binds with high affinity to this transporter. [3H]TBZOH has been used as a ligand to label VMAT2 in human, bovine and rodent brain. In this study we characterized the pharmacodynamic and pharmacokinetic parameters of [3H]TBZOH binding in human platelets as compared to rat brain. The density (Bmax) and affinity (Kd) of [3H]TBZOH specific binding was assessed by Scatchard analysis. Association and dissociation rate constants (k(on), K(off)) were assessed by kinetic binding studies. In this study high-affinity and saturable binding sites for [3H]TBZOH were demonstrated in human platelets. Both the affinity of [3H]TBZOH to its binding site in platelets (Kd = 3.2+/-0.5 nM) and the kinetic rate constants (K(on) = 2.8 x 10(7) M(-1) min(-1); K(off) = 0.099 min(-1)) were similar to that in rat brain (Kd(striatum) = 1.5 nM; Kd(cerebral cortex) = 1.35 nM; K(on) = 2 x 10(7) M(-1) min(-1); K(off) = 0.069 min(-1)). Only the VMAT2 blockers tetrabenazine and reserpine inhibited [3H]TBZOH specific binding.
机译：本研究表明，人血小板不仅可以用作质膜5-羟色胺转运蛋白，还可以用作囊泡单胺转运蛋白的可接近的外周模型。囊泡单胺转运蛋白（VMAT2）负责单胺在突触囊泡中的积累。 VMAT2与质膜转运蛋白的区别在于，它以几乎相同的亲和力识别5-羟色胺，组胺，去甲肾上腺素和多巴胺。二氢丁苯那嗪（TBZOH）是一种非常有效的VMAT2抑制剂，与该转运蛋白具有高亲和力。 [3H] TBZOH已被用作在人，牛和啮齿动物脑中标记VMAT2的配体。在这项研究中，我们表征了与大鼠大脑相比，人血小板中[3H] TBZOH结合的药效学和药代动力学参数。通过Scatchard分析评估[3H] TBZOH特异性结合的密度（Bmax）和亲和力（Kd）。通过动力学结合研究评估缔合和解离速率常数（k（on），K（off））。在这项研究中，在人血小板中证明了[3H] TBZOH的高亲和力和饱和结合位点。 [3H] TBZOH与其在血小板中的结合位点的亲和力（Kd = 3.2 +/- 0.5 nM）和动力学速率常数（K（on）= 2.8 x 10（7）M（-1）min（-1） ）; K（off）= 0.099 min（-1））与大鼠脑中的相似（Kd（纹状体）= 1.5 nM; Kd（大脑皮层）= 1.35 nM; K（on）= 2 x 10（7） M（-1）min（-1）; K（off）= 0.069 min（-1））。仅VMAT2阻断剂丁苯那嗪和利血平抑制[3H] TBZOH特异性结合。

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