Isolation of a Family of Organic Anion Transporters from Human Liver and Kidney

Novel liver-specific organic anion transporter OAT7 that operates the exchange of sulfate conjugates for short chain fatty acid butyrate

“…OAT7 cDNA consisted of 2342 base pairs and had an open-reading frame of 1662 base pairs encoding a 554-amino-acid-residue protein. The database search revealed that the identical nucleotide sequence was deposited under the name of SLC22A9/hUST3 (AB062418, GenBank) and hOAT4, 14 which were not functionally characterized. Because we and others already identified and functionally characterized organic anion transporters OAT4, 25 Oat5, 30 and Oat6, 32 we renamed this newly functionally characterized transporter as OAT7 to avoid confusion.…”

“…We identified various DNA sequences or fragments that showed homology to those of the genes for human OATs (hOATs) 14,[24][25][26][27] by searching the publicly available human genome database 23 using the BLAST program (www.ncbi.nlm.nih. gov/BLAST).…”

“…6 For sodium-independent uptake, organic anion-transporting polypeptides (OATPs) of the SLC21 (SLC0) family, such as OATP-B, 7,8 OATP-C, [9][10][11] and OATP8, 12,13 mediate the transport of a variety of organic anions such as sulfobromophthalein, bile salts, and sulfate-conjugated steroid hormones, although their driving forces are still unclear. In addition, organic anion transporter 2 (OAT2) in the SLC22 family mediates the transport of organic anion such as para-aminohippurate, 14 prostaglandins, 15 zidovudine, 16 tetracycline, 17 and salicylates 18 in a sodium-independent manner. Recently, Kobayashi et al 19 have reported that it also mediates the transport of steroid sulfates as well as several drugs.…”

Identification of a New Urate and High Affinity Nicotinate Transporter, hOAT10 (SLC22A13)

“…Recently it was found that rat Oat5 exchanges ES against succinate (51). The human ortholog of OAT5 is exclusively expressed in the liver (52), indicating that hOAT10 is the first identified human renal OAT, which uses succinate as a driving force. Consequently, we suggest that hOAT10 is functionally connected to NaDC-1 (sodium dicarboxylate cotransporter 1), which provides the succinate gradient.…”

Resistance to antifolates

“…Hence, FRs may be important only when the RFC function is very low, and/or there is very high receptor expression, and the drug has a moderate or high affinity for the receptor. Recently, several organic anion carriers, expressed in the liver and kidney, have been shown to transport MTX, some with affinities comparable to that of RFC (Saito et al, 1996;Masuda et al, 1999;Sun et al, 2001;Russel et al, 2002). There is no evidence as yet indicating that these carriers are widely expressed in malignant cells and play a role in drug resistance.…”