提出的复审甲状腺甲状腺过氧化物酶的失活老鼠丙硫氧嘧啶。
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Taurog, Dorris毫升
提出的复审甲状腺甲状腺过氧化物酶的失活老鼠丙硫氧嘧啶。
内分泌学。1989年6月,124 (6):3038 - 42。
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2656250 (在PubMed]
- 文摘
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抗甲状腺药物6-propylthiouracil (PTU)以前所示我们实验室有一个出人意料的长期抑制作用在大鼠的甲状腺碘化。18小时后注入一个相对较小的剂量,碘化甲状腺中仍被超过90%。我们之前建议长期的抑制作用可能是由于甲状腺过氧化物酶(TPO)失活反应之前显示在特定条件下发生在体外碘化系统含有高纯度传真照片。然而,我们之前使用的分析方法研究并没有排除这种可能性,足够PTU仍在甲状腺即使18 h抑制TPO-catalyzed碘化的可逆的机制。一种改进的分析方法的发展,基于高效液相色谱法,让我们重新审视长期抑制作用的机制PTU在大鼠甲状腺碘化。老鼠注射35 [s] PTU (1 mumol / BW) 100克、和超滤液准备从他们的均质甲状腺由高效液相色谱分析。主要的35 s-labeled代谢物被确定为硫酸/亚硫酸盐,PTU亚磺酸盐,和PTU磺酸盐。然而,即使经过18 h,大量的不变(35 s] PTU也在场。的计算平均浓度剩余PTU 20 microM,足够高水平解释观察到的抑制碘化的基础上一个可逆的机制。实验也进行检查35 s间隔后的intrathyroidal分布[35 s] PTU的注入。 All of the oxidation products of PTU showed marked increases between 2 and 16 h after injection. Based on our view that TPO is the major mediator of intrathyroidal metabolism of PTU, this observation is inconsistent with our previous proposal that TPO is inactivated after PTU injection. The results of the present study, therefore, lead us to withdraw our previous suggestion that TPO is inactivated after injection of PTU into rats. It is more likely that inhibition of iodination by PTU in the rat thyroid involves competition between PTU and tyrosyl residues of thyroglobulin for oxidized iodine, comparable to the reversible mechanism of inhibition observed in the TPO model system.