The role of high density lipoproteins in the biodistribution of two radioiodinated probes in the rat.
The role of high density lipoproteins in the biodistribution of two radioiodinated probes in the rat.
复制标题
高密度脂蛋白在大鼠体内两种放射性碘探针的生物分布中的作用。
DOI：
10.1016/0041-008x(85)90266-2
复制
发表时间：
1985
影响因子：
3.8
通讯作者：
Counsell,RE
中科院分区：
文献类型：
--
作者：
Pohland,RC;Counsell,RE
我们选择了两种~(125)I标记的探针，~(125)I-油酸胆固醇酯(~(125)I-CO)和~(125)I-油酸胆固醇酯(~(125)I-CO)，~(125)I-~(125)I-油酸胆固醇(~(125)I-CO)和~(125)I-~(125)D(~(125)I-D~(-D))，研究了脂蛋白在药物处置中的作用，并考察了~(125)I-油酸胆固醇(~(125)I-CO)和~(125)I-~(125)D(~(125)I-~(-D)D)在药物处置中的作用，以及它们将外来分子导向特定组织的能力。利用体内和体外技术将这些探针与大鼠高密度脂蛋白(HDL)联系起来。组织分布研究表明，预先将~(125)I-CO掺入大鼠高密度脂蛋白可增加大鼠肾上腺对~(125)I-CO的摄取，当该制剂用于4-氨基吡唑-(3，4-d)-嘧啶(4-APP)引起的降血脂动物时，这种摄取显著增强。用125I-CO标记的高密度脂蛋白的乙酰化提供了证据，表明观察到的肾上腺摄取是通过受体介导的过程。与这些结果相反，先前125I-DDD与大鼠高密度脂蛋白的关联并没有改变这种化合物在正常或低血脂动物的肾上腺组织中蓄积的能力。用聚丙烯酰胺凝胶电泳法(PAGE)检测~(125)I-CO和~(125)I-DDD与大鼠高密度脂蛋白结合的稳定性。这些结果表明，~(125)I-CO与高密度脂蛋白的亲脂核心有关，而~(125)I-DDD似乎与高密度脂蛋白的表面成分部分相关。表面成分与稳定的o，p‘-DDD的饱和提供了数据，表明这种与载脂蛋白的结合可能扰乱正常的受体介导的摄取过程。这些研究表明，脂蛋白可能影响脂类化合物的分布和组织摄取，反之，亲脂分子可以影响脂蛋白的代谢命运。总体结果取决于这些亲脂化合物与脂蛋白结合的性质，仅凭分子结构是很难预测的。
Two radioiodinated probes,125I-cholesteryl oleate (125I-CO), a derivative of a natural constituent of lipoproteins, and 1-(2-chlorophenyl)-1-(4[125I]iodophenyl)-2,2-dichloroethane (125I-DDD), an analog of the adrenolytic drug o,p′-DDD (mitotane), were selected to study the role of lipoproteins in drug disposition and to examine the ability of these vehicles to direct foreign molecules to specific tissues. In vivo and in vitro techniques were utilized to associate these probes with rat high density lipoproteins (HDL). Tissue distribution studies indicated that prior incorporation of125I-CO into rat HDL increased the uptake of125I-CO by rat adrenal, which was dramatically enhanced when this preparation was administered to animals made hypolipidemic with 4-aminopyrazolo-(3,4-d)-pyrimidine (4-APP). Acetylation of HDL labeled with125I-CO provided evidence that the observed uptake into the adrenal was via a receptor-mediated process. In contrast with these results, prior association of125I-DDD with rat HDL failed to alter the ability of this compound to accumulate in adrenal tissue of normal or hypolipidemic animals. Polyacrylamide gel electrophoresis (PAGE) was utilized to examine the stability of the association of125I-CO and125I-DDD with rat HDL. These results suggested that125I-CO was associated with the lipophilic core of HDL, whereas125I-DDD appeared to be partially associated with the suface components of HDL. Saturation of surface components with stable o,p′-DDD offered data to suggest that this binding to apoproteins may disrupt the normal receptor-mediated uptake process. These studies indicate that lipoproteins may effect the distribution and tissue uptake of lipophilic compounds and, conversely, lipophilic molecules can effect the metabolic fate of lipoproteins. The overall result is dependent upon the nature of the association of these lipophilic compounds with lipoproteins which is difficult to predict on the basis of molecular structure alone.