High impact information on Slco2a1

• The protein encoded by the matrin F/G complementary DNA is thus preferably called PGT because it is likely to function as a prostaglandin transporter [1].
• Because PGT expression is especially high in this tissue, it is likely that PGT mediates the membrane step in PG clearance by the pulmonary circulation [2].
• The PGT substrate specificity and inhibitor profile match remarkably well with earlier in situ studies on the metabolic clearance of PGs by rat lung [2].
• However, when PGE2 undergoes first release and then PGT-mediated reuptake, significant oxidation takes place, suggesting that PGT imports PGE2 into the prostaglandin dehydrogenase compartment [3].
• We characterized this system further using the collecting duct cell line Madin-Darby canine kidney (MDCK), which retains COX-2 and prostaglandin dehydrogenase expression but which has lost PGT expression [3].

Biological context of Slco2a1

• We previously found that the binding site of PGT is formed, at least in part, by its membrane-spanning segments [Chan, B. S. (1999) J. Biol. Chem. 274, 25564-25570] [4].
• The nucleotide sequences predict a protein of 682 amino acids with moderate sequence similarity to LST-1, the oatp family, and the prostaglandin transporter [5].

Anatomical context of Slco2a1

• To gain insight into the possible function of the PGT in this tubule segment, we tagged rat PGT with green fluorescent protein at the COOH terminus and generated stable PGT-expressing Madin-Darby canine kidney cell lines [6].
• The PG transporter (PGT) is expressed in subapical vesicles in the kidney collecting duct [6].
• Rat PGT was transiently expressed in HeLa cells, the timed uptake of tracer PGE2 was determined in the presence of various concentrations of unlabeled prostanoids; and the resulting inhibitory constants (Ki) were determined by curve-fitting [7].
• These results with the cloned rat PGT are very similar to those previously reported in the in vitro perfused rat lung and indicate that PGT probably represents the predominant route by which certain prostanoids, including F2 isoprostanes, are transported across plasma membranes [7].
• Augmented heme oxygenase-1 induces prostaglandin uptake via the prostaglandin transporter in micro-vascular endothelial cells [8].

Associations of Slco2a1 with chemical compounds

• We propose that endogenous PGT is exocytically inserted into the collecting duct apical membrane, where it could control the concentration of luminal PGs [6].
• PGE2 and PGF2 alpha, both known to be transported, had similar affinities for PGT (Ki = 49-50 nM) [7].
• When PG15DH was coexpressed with PGT in these epithelial monolayers, about half of the PGE2 taken up apically was oxidized to 13, 14-dihydro, 15-keto-PGE2, which in turn exited the cells nondirectionally into both the apical and basolateral compartments [9].
• PGT is a broadly expressed transporter of prostaglandins (PGs) and thromboxane that is energetically poised to take up prostanoids across the plasma membrane [10].
• Here we found that modification of positively charged residues on wild-type PGT by arginine- and lysine-specific reagents significantly inhibited transport [4].

Other interactions of Slco2a1

• These include several transporters (Slc21a2, Slc15, Slc34a2), Kim 1, IGFbp-1, osteopontin, alpha-fibrinogen, and Gstalpha [11].

Analytical, diagnostic and therapeutic context of Slco2a1

• Immunoblotting and immunocytochemistry revealed that rat platelets also express abundant PGT [10].
• RT-PCR analysis revealed that PGT mRNA and Oatp2 mRNA are expressed in a capillary-rich fraction from rat brain [12].

References