Decreased expression of a novel prostaglandin transporter, OAT-PG, facilitates renocortical PGE₂ accumulation during rat pregnancy

Background: Prostaglandin (PG)-specific organic anion transporter (OAT-PG) is a recently identified renal transporter involved in the local clearance of prostaglandin E₂ (PGE₂). Since the renal biosynthesis of PGE₂ is not increased during pregnancy, this transporter expression would affect the gestational changes in the renal PGE₂ content. Methods: Kidneys from rats at different gestational stages were used to examine gestational changes in the renocortical PGE₂ concentration. The renal expression of OAT-PG and the enzymes for PGE₂ synthesis was also examined sequentially, together with the gestational changes in renal renin production. Results: The renocortical PGE₂ concentration was significantly increased during midterm to late pregnancy, with a maximum increase of 47.6 ± 11.5% from the virgin value. Although the expression of the enzymes, such as cyclooxygenases and PG synthases, was not increased, that of OAT-PG was significantly decreased throughout pregnancy, inversely correlating with changes in the renocortical PGE₂ concentration. Renal renin production was significantly increased during pregnancy. Conclusion: This study demonstrated for the first time that the tissue PGE₂ concentration was increased in pregnant rat kidneys, which may be associated with the gestational rise in glomerular filtration rate. The decreased expression of OAT-PG was thought to be responsible for the increased tissue PGE₂ content.