Arachidonic acid metabolic pathways regulating activity of renal Na(+)-K(+)-ATPase are age dependent.
Locally formed arachidonic acid (AA) metabolites are important as modulators of many aspects of renal tubular function, including regulation of the activity of tubular Na(+)-K(+)-ATPase. Here we examined the ontogeny of the AA metabolic pathways regulating proximal convoluted tubular (PCT) Na(+)-K(+)-ATPase activity in infant and adult rats. Eicosatetraynoic acid, an inhibitor of all AA-metabolizing pathways, abolished this effect. AA inhibition of PCT Na(+)-K(+)-ATPase was blocked by the 12-lipoxygenase inhibitor baicalein in infant but not in adult rats and by the specific cytochrome P-450 fatty acid omega-hydroxylase inhibitor 17-octadecynoic acid in adult but not in infant rats. The lipoxygenase metabolite 12(S)-hydroxyeicosatetraenoic acid (HETE) and the cytochrome P-450 metabolite 20-HETE both inhibited PCT Na(+)-K(+)-ATPase in a protein kinase C-dependent manner, but the effect was significantly more pronounced in infant PCT. Lipoxygenase mRNA was only detected in infant cortex. Expression of renal isoforms of cytochrome P-450 mRNA was more prominent in adult cortex. In summary, the AA metabolic pathways that modulated the activity of rat renal proximal tubular Na(+)-K(+)-ATPase are age dependent.
Li
D
D
Department of Woman and Child Health, Pediatric Unit, Karolinska Institute, S-171 76 Stockholm, Sweden.
Belusa
R
R
Nowicki
S
S
Aperia
A
A
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D001483:Base Sequence; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D017931:DNA Primers; D012333:RNA, Messenger; D015117:5,8,11,14-Eicosatetraynoic Acid; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001092:Arachidonate 12-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D042926:Cytochrome P-450 CYP4A; D000254:Sodium-Potassium-Exchanging ATPase