Evidence for a DCCD-sensitive component of proximal bicarbonate reabsorption.
To examine the possible contribution of active H+ secretion mediated by brush border enzymes to proximal tubule HCO-3 absorption, paired reperfusions of surface proximal convoluted tubules were performed with the inhibitor dicyclohexylcarbodiimide (DCCD). In control studies using a solution devoid of HCO-3 but containing 5.5 mM glucose, 1 mM DCCD had no effect on glucose or fluid (Na+) absorption, suggesting that this inhibitor did not interfere with sodium entry at the brush border or mitochondrial energy production (ATP synthesis). In experiments using a perfusion solution containing 18-25 mM HCO-3, DCCD caused a fall in absolute CO2 absorption of approximately 15% under eucapneic conditions and 30% during acute hypercapnia. One millimole per liter amiloride (an inhibitor of the passive Na+-H+ exchanger) caused a 15% inhibition of CO2 absorption during acute hypercapnia and a disproportionately large reduction in fluid (Na+) absorption. The latter was not due to cell poisoning, since 1 mM amiloride had no inhibitory effect on fluid or glucose absorption when a HCO-3-free perfusion solution was used. Addition of 1 mM DCCD to a perfusion solution containing either 10(-3) M amiloride or 10(-4) M acetazolamide caused a significant inhibition of CO2 absorption compared with amiloride or acetazolamide alone. The observations are consistent with the view that in addition to passive Na+-H+ exchange, active transport mediated by either a H+-ATPase or a redox-driven H+ pump in the brush border contributes significantly to HCO-3 absorption in the proximal tubule.
D000042:Absorption; D000086:Acetazolamide / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002234:Carbodiimides / Q000494:pharmacology*; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology*; D004338:Drug Combinations; D004351:Drug Resistance; D005947:Glucose / Q000378:metabolism; D006935:Hypercapnia / Q000378:metabolism; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D001639:Bicarbonates; D002234:Carbodiimides; D004338:Drug Combinations; D004024:Dicyclohexylcarbodiimide; D000584:Amiloride; D005947:Glucose; D000086:Acetazolamide