Role of protein kinase C in the adaptive increase in Na-H antiporter in respiratory acidosis.
Chronic respiratory acidosis stimulates the Vmax of the renal brush border Na-H antiporter. The activation of protein kinase C (PKC) by phorbol esters stimulates the activity of the renal Na-H antiporter. In this study, the hypothesis that PKC plays a role in the adaptive increase of the renal brush border Na-H antiporter activity to respiratory acidosis was tested. In vivo respiratory acidosis was associated with an increase in in vitro Na-H antiporter activity and also with an increase in brush border membrane PKC activity, without changes in PKC activity in cytosol or basolateral membranes. Na-H antiporter activity, assessed as the amiloride-sensitive component of 22Na uptake, was measured in cultured proximal tubule cells exposed to 10% CO2 for 48 h. Na-H antiporter activity was significantly higher in cells exposed to 10% CO2 than in those exposed to 5% CO2. To evaluate the role of PKC, cultured cells were depleted of PKC by exposure to the active phorbol ester phorbol 12-myristate 13-acetate (PMA; 10(-7) or 10(-6) M) for 48 h before exposure to 10% CO2. In the presence of 10% CO2, Na-H antiporter activity was significantly lower in PKC-depleted cells than in control. In addition, sphingosine, an inhibitor of PKC, also prevented the adaptation of the Na-H antiporter to 10% CO2 as compared with 5% CO2. In cells treated with the inactive analog 4 alpha-PMA, 22Na uptake was not different than that in control. PMA-treated cells also had a decrease in Na-H antiporter activity during exposure to 5% CO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Pahlavan
P
P
Section of Nephrology, University of Illinois at Chicago 60612.
Wang
L J
LJ
Sack
E
E
Arruda
J A
JA
D000142:Acidosis, Respiratory / Q000378:metabolism*; D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D006935:Hypercapnia / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017923:Sodium-Hydrogen Exchangers; D011493:Protein Kinase C; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate