Regulation of rat proximal tubule Na/H exchange by protein kinase C.
The effect of protein kinase C (PKC) activation on fluid and bicarbonate transport in renal tubules has been discussed controversially. Stimulation and inhibition have been shown to depend on factors such as experimental model and exposure time to the mediator of enzyme activation. We studied the role of PKC activation by phorbol-12-myristate-13-acetate (PMA) and by 1,2-dioctanoyl glycerol (DOG) in proximal bicarbonate reabsorption (JHCO3-) by 'in vivo' stationary microperfusion and ion-exchange resin microelectrode determination of luminal pH. Both PMA (10(-8) mol/l) and DOG (10(-3) mol/l) added to lumen or to peritubular capillaries reduced the net JHCO3- significantly. When added to lumen, the inhibition was 44 and 32%, respectively. This reduction did not involve changes in lumen stationary pH, but was mediated by a marked increase in the halftime of luminal bicarbonate disappearance; from 4.22 +/- 0.23 to 6.27 +/- 0.51 s with PMA and from 3.90 +/- 0.25 to 6.33 +/- 0.48 s with DOG. This effect was intensified by 10(-6) mol/l okadaic acid, a phosphatase inhibitor (inhibition of JHCO3- increased to 61%), and reduced by 30% by 10(-6) mol/l H7, an inhibitor of PKC. H89, a protein kinase A inhibitor, did not affect the inhibitory action of PMA. Our data suggest that PKC activation reduces the rate of H ion secretion (bicarbonate reabsorption) in convoluted segments of rat renal proximal tubules and that phosphorylation of the Na+/H+ exchanger by this kinase is the cause of the reduction in net secretion of H ions.
Rebouças
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Departamento de Fisiologia e Biofisica, Universidade de São Paulo, Brazil.
Malnic
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D000143:Acids; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010703:Phorbol Esters / Q000494:pharmacology*; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects* / Q000378:metabolism
D000143:Acids; D001639:Bicarbonates; D004791:Enzyme Inhibitors; D010703:Phorbol Esters; D017923:Sodium-Hydrogen Exchangers; C057360:5-(N,N-hexamethylene)amiloride; D000584:Amiloride; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010744:Phosphoric Monoester Hydrolases