Publications

• The prostaglandin transporter PGT transports PGH(2).

  Chi Y., Schuster V.L.

  Prostaglandin H(2) not only serves as the common precursor of all other PGs, but also directly triggers signals (e.g. platelet aggregation), depending on its location and translocation. The prostaglandin carrier PGT mediates the transport of several prostanoids, such as PGE(2), and PGF(2alpha). He ... >> More

  Prostaglandin H(2) not only serves as the common precursor of all other PGs, but also directly triggers signals (e.g. platelet aggregation), depending on its location and translocation. The prostaglandin carrier PGT mediates the transport of several prostanoids, such as PGE(2), and PGF(2alpha). Here we used PGT in the plasma membrane as a model system to test the hypothesis that PGT also transports PGH(2). Using wild-type and PGT-expressing MDCK cells, we show that PGH(2) uptake is mediated both by simple diffusion and by PGT. The PGH(2) influx permeability coefficient for diffusion is (5.66+/-0.63)x10(-6)cm/s. The kinetic parameters of PGH(2) transport by PGT are K(m)=376+/-34nM and V(max)=210.2+/-11.4 fmol/mg protein/s. PGH(2) transport by PGT can be inhibited by excess PGE(2) or by a PGT inhibitor. We conclude that PGT may play a role in transporting PGH(2) across cellular membranes. << Less

  Biochem. Biophys. Res. Commun. 395:168-172(2010) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Identification of lactate as a driving force for prostanoid transport by prostaglandin transporter PGT.

  Chan B.S., Endo S., Kanai N., Schuster V.L.

  We previously characterized the prostaglandin (PG) transporter PGT as an exchanger in which [(3)H]PGE(2) influx is coupled to the efflux of a countersubstrate. Here, we cultured HeLa cells that stably expressed human PGT under conditions known to favor glycolysis (glucose as a carbon source) or ox ... >> More

  We previously characterized the prostaglandin (PG) transporter PGT as an exchanger in which [(3)H]PGE(2) influx is coupled to the efflux of a countersubstrate. Here, we cultured HeLa cells that stably expressed human PGT under conditions known to favor glycolysis (glucose as a carbon source) or oxidative phosphorylation (glutamine as a carbon source) and studied the effect on PGT-mediated [(3)H]PGE(2) influx. PGT-expressing cells grown in glutamine exhibited a 2-to 4-fold increase in [(3)H]PGE(2) influx compared with the antisense control, whereas cells grown in glucose exhibited a 14-fold increase. In the presence of 10 vs. 25 mM glucose during the uptake, there was a dose-dependent increment in [(3)H]PGE(2) influx. Cis inhibition of [(3)H]PGE(2) influx occurred with lactate at physiological concentrations (apparent K(m) = 48 +/-12 mM). Preloading with lactate caused a dose-dependent trans stimulation of PGT-mediated [(3)H]PGE(2) uptake, and external lactate caused trans stimulation of PGT-mediated [(3)H]PGE(2) release. Together, these data are consistent with PGT-mediated PG-lactate exchange. Cells engaged in glycolysis would then be poised energetically for prostanoid uptake by means of PGT. << Less

  Am. J. Physiol. 282:F1097-F1102(2002) [PubMed] [EuropePMC]

• Cloning, in vitro expression, and tissue distribution of a human prostaglandin transporter cDNA(hPGT).

  Lu R., Kanai N., Bao Y., Schuster V.L.

  We recently identified a cDNA in the rat that encodes a broadly expressed PG transporter (PGT). Because PGs play diverse and important roles in human health and disease, we cloned human PGT (hPGT) from an adult human kidney cDNA library. A consensus sequence (4.0 kb) derived from several clones, p ... >> More

  We recently identified a cDNA in the rat that encodes a broadly expressed PG transporter (PGT). Because PGs play diverse and important roles in human health and disease, we cloned human PGT (hPGT) from an adult human kidney cDNA library. A consensus sequence (4.0 kb) derived from several clones, plus 3' polymerase chain reaction amplification, exhibited 74% nucleic acid identity and 82% amino acid identity compared to rat PGT. When transiently expressed in HeLa cells, a full-length clone catalyzed the transport of PGE1, PGE2, PGD2, PGF2alpha, and, to a lesser degree, TXB2. Northern blotting revealed mRNA transcripts of many different sizes in adult human heart, placenta, brain, lung, liver, skeletal muscle, pancreas, kidney, spleen, prostate, ovary, small intestine, and colon. hPGT mRNAs are also strongly expressed in human fetal brain, lung, liver, and kidney. The broad tissue distribution and substrate profile of hPGT suggest a role in the transport and/or metabolic clearance of PGs in diverse human tissues. << Less

  J. Clin. Invest. 98:1142-1149(1996) [PubMed] [EuropePMC]

  This publication is cited by 9 other entries.

• Prostaglandin transporter (OATP2A1/SLCO2A1) contributes to local disposition of eicosapentaenoic acid-derived PGE3.

  Gose T., Nakanishi T., Kamo S., Shimada H., Otake K., Tamai I.

  Eicosapentaenoic acid (EPA)-derived prostaglandin E3 (PGE3) possesses an anti-inflammatory effect; however, information for transporters that regulate its peri-cellular concentration is limited. The present study, therefore, aimed to clarify transporters involved in local disposition of PGE3. PGE3 ... >> More

  Eicosapentaenoic acid (EPA)-derived prostaglandin E3 (PGE3) possesses an anti-inflammatory effect; however, information for transporters that regulate its peri-cellular concentration is limited. The present study, therefore, aimed to clarify transporters involved in local disposition of PGE3. PGE3 uptake was assessed in HEK293 cells transfected with OATP2A1/SLCO2A1, OATP1B1/SLCO1B1, OATP2B1/SLCO2B1, OAT1/SLC22A6, OCT1/SLC22A1 or OCT2/SLC22A2 genes, compared with HEK293 cells transfected with plasmid vector alone (Mock). PGE3 uptake by OATP2A1-expressing HEK293 cells (HEK/2A1) was the highest and followed by HEK/1B1, while no significantly higher uptake of PGE3 than Mock cells was detected by other transporters. Saturation kinetics in PGE3 uptake by HEK/2A1 estimated the Km as 7.202 ± 0.595 μM, which was 22 times higher than that of PGE2 (Km=0.331 ± 0.131 μM). Furthermore, tissue disposition of PGE3 was examined in wild-type (WT) and Slco2a1-deficient (Slco2a1(-/-)) mice after oral administration of EPA ethyl ester (EPA-E) when they underwent intraperitoneal injection of endotoxin (e.g., lipopolysaccharide). PGE3 concentration was significantly higher in the lung, and tended to increase in the colon, stomach, and kidney of Slco2a1(-/-), compared to WT mice. Ratio of PGE2 metabolite 15-keto PGE2 over PGE2 concentration was significantly lower in the lung and colon of Slco2a1(-/-) than that of WT mice, suggesting that PGE3 metabolism is downregulated in Slco2a1(-/-) mice. In conclusion, PGE3 was found to be a substrate of OATP2A1, and local disposition of PGE3 could be regulated by OATP2A1 at least in the lung. << Less

  Prostaglandins Other Lipid Mediat. 122:10-17(2016) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.