通过与多药物耐药性相关的蛋白质1和5运输他类药物
Suvi-Kukka Tuomi1, Feng Deng2, Mikko Neuvonen1
1Department of Clinical Pharmacology, Faculty of Medicine, University of Helsinki, Finland; Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Finland.
概括
多种药物耐药性相关蛋白 (MRP) 1和5在骨肌中运输和皮塔. 这可能会减少肌细胞中他类药物的暴露,并可能防止与这些降胆固醇药物相关的肌肉毒性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 类他类药物对于高胆固醇血症治疗至关重要,但可能导致与肌肉相关的副作用.
- 多重耐药性相关蛋白 (MRPs),特别是MRP1和MRP5,存在于骨肌中,可能影响细胞内药物水平.
研究的目的:
- 调查MRP1和MRP5对各种他类药物的运输活动.
- 确定MRP1和MRP5是否在他类药物诱导的肌肉毒性中起作用.
主要方法:
- 使用囊泡运输试验研究了MRP1和MRP5.5对他类药物的吸收.
- 使用液体染色学并联质谱法量化了他酸度.
- 对于运输的他类药物,确定了体外清除率 (CLin vitro) 和明显亲和度 (Km).
主要成果:
- MRP1 携带了流沙沙丁的两个反体.
- 在MRP5中,流星和皮塔星被运输,但阿托星没有被运输.
- 普拉瓦斯塔丁,罗斯瓦斯塔丁和西姆瓦斯塔丁酸不是MRP1或MRP5.5的基质.
结论:
- MRP1促进流沙他丁的运输,而MRP5运输流沙他丁和皮塔瓦沙他丁.
- 骨肌中MRP1和MRP5的表达表明它在调节肌细胞暴露于这些他类药物中的作用.
- 这种相互作用可能提供一种保护机制,防止与他类药物相关的肌肉毒性.
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