Decreased Expression of a Novel Prostaglandin Transporter, OAT-PG, Facilitates Renocortical PGE₂ Accumulation during Rat Pregnancy

Abstract

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.

Pitting type of pretibial edema in a patient with silent thyroiditis successfully treated by angiotensin II receptor blockade

“…Previously, Peti-Peterdi et al demonstrated in in vitro studies that the increased expression of cyclooxygenase-2 (COX-2) and the production of pros-taglandin E 2 (PGE 2 ) in macula densa cells stimulate renal renin synthesis from juxtaglomerular cells [23–25]. Recently, we have further demonstrated in animal studies that the increase in renal PGE 2 was actually associated with the increase in local renin production [26]. Since thyroid hormone is known to positively regulate the renal expression of COX-2 and PGE 2 [27], this hormone was thought to stimulate renal renin synthesis by increasing the local production of COX-2 and PGE 2 in the kidney.…”