Effects of dietary protein on eicosanoid production in rat renal tubules

The effects of dietary protein on the in vitro production of prostaglandin (PG) E2, 6-keto PGF1alpha, and thromboxane B2 (TxB2) were examined in cortical and medullary tubules from rats fed a low (6% casein) or a high (40% casein) protein diet for approximately 8 weeks. PGE2 was a major eicosanoid produced by rat renal tubules (PGE2 > TxB2 > 6-keto PGF1alpha). Medullary tubules produced significantly greater amounts of PGE2, 6-keto PGF1alpha, and TxB2 than cortical tubules. The activity of phospholipase (PL) A2 and PLC and the levels of cyclooxygenase (COX) were significantly greater in medullary tubules than in cortical tubules. The production of eicosanoids may be increased in medullary versus cortical tubules via the greater activity of these enzymes involved in eicosanoid formation. Although there were no substantial differences in the production of PGE2, 6-keto PGF1alpha, and TxB2 between cortical tubules from rats fed a low- or a high-protein diet, significant increases in the synthesis of the three eicosanoids were observed in medullary tubules from rats fed a high- versus a low-protein diet. The activity of membrane-bound PLA2 and PLC and the levels of COX were not also substantially different between cortical tubules from rats fed a low- or a high-protein diet. However, medullary tubules had significantly greater activity of membrane-associated PLA2 and COX in rats fed a high-protein diet than in those fed a low-protein diet. The activity of PLC was comparable in medullary tubules from rats fed a low- or a high-protein diet. We conclude that a high protein intake selectively enhances eicosanoid production in rat medullary tubules probably via activation of the PLA2-COX pathway.