OAT, OATP和MRP药物转运体与遥感和信号理论。

IF 11.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Sanjay K Nigam, Jeffry C Granados
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引用次数: 9

摘要

有机阴离子(如药物、代谢物、信号分子、营养物质、抗氧化剂、肠道微生物组产物)在组织和体液之间的协调运动在很大程度上取决于有机阴离子转运体(OATs)[溶质载体22 (SLC22)]、有机阴离子转运多肽(OATPs)[溶质载体有机(SLCO)]和多药耐药蛋白(MRPs) [atp结合盒,亚家族C (ABCC)]。根据底物的范围,这些家族中的转运蛋白可以被认为是多特异性、寡特异性或(相对)单特异性。在表达模式的背景下对这些转运蛋白的系统生物学分析表明,它们是参与器官间和生物间通信的网络中的枢纽。遥感和信号理论解释了药物转运体、药物代谢酶和调节蛋白的协调功能如何在优化系统和局部水平的重要内源性小分子中发挥作用。我们专注于燕麦、燕麦多糖和MRPs在内源性代谢中的作用,以及它们的底物(如胆汁酸、短链脂肪酸、尿酸、尿毒症毒素)如何介导器官间和生物间的交流,并帮助维持和恢复健康和疾病状态下的体内平衡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
OAT, OATP, and MRP Drug Transporters and the Remote Sensing and Signaling Theory.

The coordinated movement of organic anions (e.g., drugs, metabolites, signaling molecules, nutrients, antioxidants, gut microbiome products) between tissues and body fluids depends, in large part, on organic anion transporters (OATs) [solute carrier 22 (SLC22)], organic anion transporting polypeptides (OATPs) [solute carrier organic (SLCO)], and multidrug resistance proteins (MRPs) [ATP-binding cassette, subfamily C (ABCC)]. Depending on the range of substrates, transporters in these families can be considered multispecific, oligospecific, or (relatively) monospecific. Systems biology analyses of these transporters in the context of expression patterns reveal they are hubs in networks involved in interorgan and interorganismal communication. The remote sensing and signaling theory explains how the coordinated functions of drug transporters, drug-metabolizing enzymes, and regulatory proteins play a role in optimizing systemic and local levels of important endogenous small molecules. We focus on the role of OATs, OATPs, and MRPs in endogenous metabolism and how their substrates (e.g., bile acids, short chain fatty acids, urate, uremic toxins) mediate interorgan and interorganismal communication and help maintain and restore homeostasis in healthy and disease states.

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来源期刊
CiteScore
27.80
自引率
0.00%
发文量
53
期刊介绍: Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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