Ontogeny of the regulation of Na+,K(+)-ATPase activity in the renal proximal tubule cell.
This study examines the ontogeny of the regulation of Na+,K(+)-ATPase activity in the proximal tubule (PT) by a first messenger, dopamine (DA), and by direct stimulation of a third messenger, protein kinase C (PKC). PT segments dissected from 10- (PT10), 15-(PT15), 20- (PT20), and 40- (PT40) d-old rats were preincubated with DA 10(-5) M, diacylglycerol (DAG) 10(-5) M (an endogenous activator of PKC), or phorbol 12,13-dibutyrate (PDBu) 10(-6) M (an exogenous activator of PKC). DA inhibited Na+,K(+)-ATPase activity in PT40. In PT20, DA also inhibited Na+,K(+)-ATPase activity, but the inhibitory effect in PT20 was less pronounced than in PT40. In PT15, DA had no effect on Na+,K(+)-ATPase activity. DAG significantly inhibited Na+,K(+)-ATPase activity in PT40. DAG also inhibited Na+,K(+)-ATPase activity in PT20, but the inhibition was slightly less pronounced than in PT40. DAG had no effect on Na+,K(+)-ATPase activity in PT15. Na+,K(+)-ATPase activity in PT40 and PT20 preincubated with PDBu was significantly lower than with vehicle. The inhibitory effect in PT20 was less pronounced than in PT40. When PT40 and PT20 were preincubated with both PDBu and 5 x 10(-5) M sphingosine, an inhibitor of PKC activation, the inhibitory effect of PDBu was abolished. In both PT40 and PT20 incubated with 4-alpha-12,13 phorbol didecanoate 10(-7) M, a phorbol ester that will not activate PKC, Na+,K(+)-ATPase activity was not different from the control. In PT10, Na+,K(+)-ATPase activity was the same after PDBu incubation and after vehicle incubation.(ABSTRACT TRUNCATED AT 250 WORDS)
Fukuda
Y
Y
Department of Pediatrics, St. Göran's Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
Bertorello
A
A
Aperia
A
A
D000375:Aging / Q000378:metabolism; D000818:Animals; D046508:Culture Techniques; D004298:Dopamine / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine