Multiple arachidonic acid metabolites inhibit sodium-dependent phosphate transport in OK cells.
The cytochrome P450-dependent monoxygenase pathway represents a major route for the metabolism of arachidonic acid (AA) in the kidney. In turn, AA metabolites have been shown to affect renal electrolyte metabolism, including sodium transport. Specifically AA, 20-HETE and 12-HETE inhibit sodium-dependent (Na+-Pi) uptake into renal culture cells, and both 12-HETE and 14,15 EET have been shown to reduce renin release from renal cortical slices. Since the bulk of Pi transport occurs in the proximal tubule (PT), and the PT is a major site of AA metabolism, we studied the effect of AA and several of its metabolites on Na+-Pi uptake into PT-like opossum kidney (OK) cells. Incubation of OK cells in AA (10(-8) M) resulted in 17% inhibition of Pi uptake. Three metabolites of omega-hydroxylation of AA induced significant decreases in Pi uptake: 19R-HETE (10(-8) M) by 36% (P=0.008), 19S-HETE (10(-8) M) by 24% (P=0.002) and 20-COOH-AA (10(-8) M), a metabolite of 20-HETE, by 25% (P<0.0001). 14,15 EET (10(-8) M), a breakdown product of AA by the epoxygenase pathway, had the greatest effect on Pi uptake in OK cells. It decreased Pi uptake by 47% (P < 0.0001). Addition of the P450 inhibitor, 7-ER (10(-8) M), to OK cells resulted in a significant stimulation (28%) of Pi uptake (P=0.016). These results indicate that these AA metabolites have a significant inhibitory effect on Na+-Pi uptake in OK cells.
Silverstein
D M
DM
Department of Pediatrics, Division of Nephrology, Albert Einstein College of Medicine, Bronx, NY, USA. DSilverst@aol.com
Barac-Nieto
M
M
Spitzer
A
A
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004573:Electrolytes / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D009893:Opossums; D010078:Oxazines / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D004573:Electrolytes; D006893:Hydroxyeicosatetraenoic Acids; D010078:Oxazines; D010710:Phosphates; D016718:Arachidonic Acid; C007649:ethoxyresorufin; C055986:19-hydroxy-5,8,11,14-eicosatetraenoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D012964:Sodium; D012083:Renin; D015126:8,11,14-Eicosatrienoic Acid