Renal cytochrome P450-related arachidonate metabolite inhibits (Na+ + K+)ATPase.
The function of the nephron, the anatomical unit of the kidney, is segmented; at least 12 segments have been identified that differ in their morphology, transport properties and hormonal responsiveness. The medullary portion of the thick ascending limb of the loop of Henle (mTALH) has one of the highest concentrations of (Na+ + K+)ATPase found in mammalian tissues, reflecting the importance of this nephron segment in the regulation of extracellular fluid volume, as active sodium transport is driven by (Na+ + K+)ATPase. Here, in cells derived primarily from the mTALH of the outer medulla of rabbit kidney, we have identified a cytochrome P450-dependent monooxygenase system which metabolizes arachidonic acid to two biologically active oxygenated products; one of the products inhibits (Na+ + K+)ATPase and the other relaxes blood vessels. We report that formation of these oxygenated arachidonate metabolites is stimulated by arginine vasopressin (AVP) and salmon calcitonin (SCT).
Schwartzman
M
M
Ferreri
N R
NR
Carroll
M A
MA
Songu-Mize
E
E
McGiff
J C
JC
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D002116:Calcitonin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014664:Vasodilation; D014882:Water-Electrolyte Balance
D001095:Arachidonic Acids; D001127:Arginine Vasopressin; D016718:Arachidonic Acid; D002116:Calcitonin; D003577:Cytochrome P-450 Enzyme System; D000254:Sodium-Potassium-Exchanging ATPase