Interactions of human- and rat-organic anion transporters with pravastatin and cimetidine

被引：53

作者：

Khamdang, S

Takeda, M

Shimoda, M

Noshiro, R

Narikawa, S

Huang, XL

Enomoto, A

Piyachaturawat, P

Endou, H ^{[1
]}

机构：

[1] Kyorin Univ, Sch Med, Dept Pharmacol & Toxicol, Tokyo 1818611, Japan

[2] Mahidol Univ, Fac Sci, Dept Physiol, Bangkok 10400, Thailand

[3] Tokyo Univ Agr & Technol, Fac Agr, Dept Vet Med, Tokyo 1830054, Japan

[4] Fuji Biomedixs Co, Kobuchizawa Labs, Yamanashi 4080044, Japan

来源：

JOURNAL OF PHARMACOLOGICAL SCIENCES | 2004年 / 94卷 / 02期

关键词：

organic anion transporter; pravastatin; cimetidine;

D O I：

10.1254/jphs.94.197

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We have elucidated the interactions of human and rat organic anion transporters (hOATs and rOATs) with pravastatin and cimetidine. Pravastatin inhibited hOAT1/rOAT1, hOAT2/rOAT2, hOAT3/rOAT3, and hOAT4. The mode of inhibition was noncompetitive for hOAT1 and hOAT2, whereas it was competitive for hOAT3 and hOAT4. Cimetidine also inhibited hOAT1/rOAT1, hOAT3 /rOAT3, and hOAT4. The mode of inhibition was a combination of competitive and noncompetitive manners for hOAT1, whereas it was competitive for hOAT3. The effects of OAT inhibitors on OAT1, OAT2, and OAT3 exhibited some but not so remarkable interspecies differences between humans and rats. In conclusion, we have characterized pravastatin and cimetidine as OAT inhibitors.

引用

页码：197 / 202

页数：6

共 17 条

[11] Kojima R, 2002, J AM SOC NEPHROL, V13, DOI 10.1681/ASN.V134848
[12] MALLORYMJ, 2000, BASIC CLIN PHARM, P581
[13] Motohashi H, 2002, J AM SOC NEPHROL, V13, DOI 10.1681/ASN.V134866
[14] Properties and regulation of organic cation transport in freshly isolated human proximal tubules
Pietig, G
Mehrens, T
Hirsch, JR
Çetinkaya, I
Piechota, H
Schlatter, E
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (36) : 33741 - 33746
[15] Molecular aspects of renal anionic drug transport
Russel, FGM
Masereeuw, R
van Aubel, RAMH
[J]. ANNUAL REVIEW OF PHYSIOLOGY, 2002, 64 : 563 - 594
[16] SEKINE T, 1999, CLIN EXP NEPHROL, V3, P237
[17] Characterization of organic anion transport inhibitors using cells stably expressing human organic anion transporters
Takeda, M
Narikawa, S
Hosoyamada, M
Cha, SH
Sekine, T
Endou, H
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2001, 419 (2-3) : 113 - 120

← 1 2 →