Cytochrome P450-dependent arachidonate metabolites affect renal transport in the rabbit

Arachidonic acid (AA) inhibited 86Rb uptake in a dose-dependent manner in rabbit medullary tubules representing the thick ascending limb of the loop of Henle (mTALH). We have shown that CoCl2 treatment of rabbits reduced renal AA metabolism by cytochrome P450-dependent enzymes (P450). After CoCl2 treatment, AA was without effect on 86Rb uptake in mTALH cells. However, the two principal P450-AA metabolites produced by the mTALH, 20-HETE and 20-COOH-AA, inhibited 86Rb uptake in a dose-dependent manner in mTALH cells whether obtained from control or CoCl2-treated rabbits. These data support our hypothesis that CoCl2 treatment impairs ion transport function of mTALH cells by blocking cytochrome P450-AA metabolism, a blockade circumvented by the relevant P450-AA metabolites.