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Transport of nicotinate by human organic anion transporters of SLC22 family
Author(s) -
He Xin,
Anzai Naohiko,
Ljubojevic Marija,
Ueno Takeshi,
Fukutomi Toshiyuki,
Sakata Takeshi,
Sabolic Ivan,
Hirata Taku,
Endou Hitoshi,
Kanai Yoshikatsu
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1143-d
Subject(s) - probenecid , organic anion transporter 1 , chemistry , ketoprofen , ibuprofen , organic anion , salicylic acid , transporter , biochemistry , drug , pharmacology , glibenclamide , organic anion transporting polypeptide , gene , endocrinology , biology , chromatography , ion , organic chemistry , diabetes mellitus
Nicotinate has been used as a lipid‐lowering agent producing beneficial changes in serum lipids for atherosclerosis regression. The purpose of this study is to elucidate the molecular mechanisms underlying the transport of nicotinate by human organic anion transporters (OATs) of SLC22 family stably expressed in a mouse cell line derived from renal proximal tubule S 2 segment. Among OATs tested (hOAT1‐4), hOAT1 and hOAT2 mediated a time‐ and concentration‐dependent uptake of nicotinate. We focused on the study of hOAT2 because it showed higher activity in nicotinate transport compared with hOAT1. hOAT2‐mediated nicotinate uptake showed structural specificity, and was inhibited by some organic anions such as indocyanine green, glibenclamide, and probenecid and some NSAIDs (salicylic acid, diclofenac, ketoprofen, indomethacine, and ibuprofen). The identicication of nicotinate transporter will contribute to understanding the molecular basis of such a drug‐drug interaction as salicylate‐induced increase in serum nicotinate level.