K+ alters cytochrome P-450-dependent arachidonate metabolism by rabbit renomedullary cells.
We studied the effects of K+ on cytochrome P-450-dependent arachidonic acid (P450-AA) metabolism by cells isolated from the rabbit medullary thick ascending limb of Henle's loop (MTAL) by varying K+ from 0 to 7.5 mM in the incubating medium because of the known effects of K+ on AA metabolism. Rabbit MTAL cells convert AA to metabolites that segregate into two peaks (P1 and P2) on reverse-phase high-performance liquid chromatography; P1 contains vasodilator material and P2 an inhibitor(s) of Na(+)-K(+)-ATPase activity. Formation of P450-AA metabolites by MTAL was enhanced by reducing external K+ (P less than 0.01) and was not affected by changes in external Cl- but was dependent on the presence of intact MTAL cells, suggesting that P450-AA metabolism was related to altering ion fluxes and/or cell volume changes. The effects of altered external K+ on MTAL P450-AA metabolism could be nullified by increasing K+ intake before killing the rabbits. Evidence for the absence of a direct effect of zero K+ on Na(+)-K(+)-ATPase was provided by the demonstration that ouabain failed to affect AA metabolism in MTAL cells. We conclude that P450-AA metabolism by MTAL cells can be influenced either directly by altering external K+ in the incubate or indirectly by changing dietary K+ before killing the rabbits. Furthermore, MTAL P450-AA metabolism was independent of changes in external Cl- and Na(+)-K(+)-ATPase activity.
Carroll
M A
MA
Department of Pharmacology, New York Medical College, Valhalla 10595.
Louzan
M
M
McGiff
J C
JC
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D007679:Kidney Medulla; D007684:Kidney Tubules / Q000378:metabolism*; D008138:Loop of Henle / Q000166:cytology / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D011817:Rabbits
D001095:Arachidonic Acids; D002712:Chlorides; D016718:Arachidonic Acid; D010042:Ouabain; D003577:Cytochrome P-450 Enzyme System; D011188:Potassium