Transport of nicotinate by human organic anion transporters of SLC22 family

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 S2 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.