A structure-relationship study of the transport mechanism of polyamine compounds across plasma membrane.

在这项研究中，我们利用大鼠肠道刷缘和基侧膜小泡，以及大鼠肾刷缘小泡，研究了多阳离子药物(二、三和四胺类化合物)跨质膜转运机制的结构关系。聚阳离子药物通过肠道刷状缘膜的转运机制二胺类化合物的初始转运速率与其亲脂性之间有很好的相关性。另一方面，三胺和四胺化合物的转运速率与二胺化合物几乎相同，尽管三胺和四胺化合物的亲脂性远低于二胺化合物。呋喃霉素诱导的钾扩散电位(内负值)刺激膜泡对二胺类化合物的初始摄取，二胺类化合物的亲脂性与扩散电位依赖的转运量之间有很好的相关性。然而，由于它们极低的亲脂性…更多的TY、三胺和四胺化合物不受扩散电位的影响。此外，膜表面电位在所有聚阳离子化合物的转运过程中起着共同的作用。聚阳离子药物通过肠基外侧膜的转运机制大鼠肠基侧膜中有一种特殊的二胺类化合物腐胺的载体。这种载体的驱动力是向内的Na+梯度，并运输到细胞内。载体介导的腐胺转运被其他二胺化合物抑制。由于三胺和四胺化合物对转运没有影响，该载体只能识别二胺化合物。聚阳离子药物通过肾刷状缘膜的转运机制由于精胺和三胺类化合物，四胺类化合物能反式刺激大鼠肾基底外侧膜小泡摄取精胺，小泡是四胺类化合物的特异性载体。此外，在体外研究中，曲宁宁的肾脏清除速度快于肌酐清除。这些数据表明，这种转运系统有助于肾近端小管中毒胺的分泌。较少

In this study, we investigated the structure-relationship of the transport mechanism of polycationic drugs (di-, tri-and tetraamine compounds) across plasma membrane using rat intestinal brush-border and basolateral membrane vesicles, and rat renal brush-border membrane vesicles.1. Transport mechanism of polycationic drugs across intestinal brush-border membraneA good correlation between the initial transport rate of diamine compounds and their lipophilicities. On the other hand, the transport rate of tri-and tetraamine compounds was almost same as diamine compound, although the lipophilicity of tri-and tetraamine were much lower than diamine compounds. A valinomycin induced potassium-diffusion potential (inside-negative) stimulated the initial uptake of diamine compounds by membrane vesicles, and a good correlation was observed between the lipophilicity and the amount of diffusion-potential dependent transport of diamine compounds. However, because of their extremely lower lipophilici … More ty, tri-and tetraamine compounds werenot affected by the diffusion potential. Furthermore, membrane surface potential playd a common role in the transport of all polycationic compounds.2. Transport mechanism of polycationic drugs across intestinal basolateral membraneThere was a specific carrier for putrescine, a diamine compound, in the ratintestinal basolateral membrane. The driving force of this carrier was an inward Na^+ gradient, and transport into the cell. Carrier-mediated transport of putrescine was inhibited by other diamine compounds. Because of that tri- and tetraamine compounds did not affect to the transport, this carrier would recognize only diamine compounds.3. Transport mechanism of polycationic drugs across renal brush-border membraneBecause of spermine and trientine, tetraamine compounds, trans-stimulated the uptake of spermine by rat renal basolateral membrane vesicles, a specific carrier for tetraamine compounds existed in this membrane. Moreover, in-vitro study, the renal clearance of trientine was faster than creatinine clearance. These data suggest that this transport system contributes to the secretion of tetraamines in the kidney proximal tubule. Less