Molecular Biological Studies on Relationships between Changes in Renal Tubular Transporter Gene Expressions and Deterioration of Drug Excretory Functions in Renal Diseases

肾病肾小管转运蛋白基因表达变化与药物排泄功能恶化关系的分子生物学研究

• 批准号: 14370781
• 负责人: SAITO Hideyuki
• 金额: $ 7.49万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370781/
• 关键词: Drug transporter; Renal excretion; Renal tubular dysfunction; Nephrotoxicity; Dosage regimen; Renal failure; 尿細管分泌; 有機アニオン; 有機カチオン; 投与設計; アニオン性薬物; カチオン性薬物; 遺伝子発現

The proximal tubules of kidney play a pivotal role in limiting or preventing toxicity by secreting organic anions and cations into urine. Organic ion transporter family(SLC22A) appeared to mediate renal secretion of these molecules. Organic anion transporters, OAT-K1 and OAT-K2 could serve as multispecific transporters, mediating transport of a wide variety of endogenous substances and xenobiotics. The levels of urinary excretion of dmetidine was reduced under cronic renal failure(CRF) partiy due to the reduced expression of rOCT2, and the lowered plasma level of testosterone was suggested to be responsible for the depressed rOCT2 expression in CRF. hOAT3 was suggested to play an important role for anionic drug secretion in patients with renal diseases and that the expression levels of drug transporters may be related to the alteration of renal drug secretion.

肾近端小管通过将有机阴离子和阳离子分泌到尿液中，在限制或预防毒性方面发挥着关键作用。有机离子转运体家族(SLC22A)似乎参与了肾脏对这些分子的分泌。有机阴离子转运体OAT-K1和OAT-K2可以作为多特异性转运体，介导多种内源物质和外源物质的转运。慢性肾功能衰竭(CRF)患者尿中dmetidine排泄量减少与rOCT2表达减少有关，血浆睾酮水平降低可能是CRF患者rOCT2表达下降的原因之一。提示hOAT3在肾脏疾病患者的阴离子药物分泌中起重要作用，药物转运蛋白的表达水平可能与肾脏药物分泌的改变有关。

项目成果

Decreased expression of glucose and peptide transporters in rat remnant kidney.

• DOI: 10.2133/dmpk.19.41
• 发表时间: 2004-02-01
• 期刊: Drug metabolism and pharmacokinetics
• 影响因子: 2.1
• 作者: Nakamura, Nobuhiko;Masuda, Satohiro;Inui, Ken-ichi
• 通讯作者: Inui, Ken-ichi

Habu, Y., et al.: "Decreased activity of basolateral organic ion transports in hyperuricemic rat kidney : roles of organic ion transporters, rOAT1, rOAT3 and rOCT2."Biochem.Pharmacol.. 66・1. 163-170 (2003)

Habu, Y., et al.：“高尿酸血症大鼠肾中基底外侧有机离子转运活性降低：有机离子转运蛋白、rOAT1、rOAT3 和 rOCT2 的作用。”Biochem.Pharmacol.. 66・1 (2003)。

Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases

• DOI: 10.1023/b:pham.0000012153.71993.cb
• 发表时间: 2004-01-01
• 期刊: PHARMACEUTICAL RESEARCH
• 影响因子: 3.7
• 作者: Sakurai, Y;Motohashi, H;Inui, K
• 通讯作者: Inui, K

Okabe, H., et al.: "Evaluation of increased bioavailability of tacrolimus in rats with experimental renal dysfunction"J.Pharm.Pharmacol.. 54・1. 65-70 (2002)

Okabe, H., et al.：“实验性肾功能障碍大鼠中他克莫司生物利用度增加的评估”J.Pharm.Pharmacol.. 54・1 (2002)。

p-Aminohippurate transport at the apical membrane in the OK kidney epithelial cell line.

OK 肾上皮细胞系顶膜上的对氨基马尿酸转运。

• 发表时间: 2002
• 期刊: Pharm.Res. 19(12)
• 作者: Habu;Y.
• 通讯作者: Y.