Molecular Mechanisms of Prostaglandin Transport

Despite the fact that prostaglandins (PGs) have low intrinsic permeabilities across the plasma membrane, they must cross it twice: first upon release from the cytosol into the blood, and again upon cellular uptake prior to oxidation. Until recently, there were no cloned carriers that transported PGs. PGT is a broadly-expressed, 12-membrane-spanning domain integral membrane protein. When heterologously expressed in HeLa cells or Xenopus oocytes, it catalyzes the rapid, specific, and high-affinity uptake of PGE2, PGF2 alpha, PGD2, 8-iso-PGF2 alpha, and thromboxane B2. Functional studies indicate that PGT transports its substrate as the charged anion. The PGT substrate specificity and inhibitor profile match remarkably well with earlier in situ studies on the metabolic clearance of PGs by rat lung. 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. Evidence is presented that PGT may play additional roles in other tissues and that there may be additional PG transporters yet to be identified molecularly.