Metabolic acidosis stimulates carbonic anhydrase activity in rabbit proximal tubule and medullary collecting duct

Both membrane-bound carbonic anhydrase (CA) (isozyme type IV) and cytosolic CA (type II) activities enhance urinary acidification. We have previously shown that chronic metabolic acidosis (CMA) accomplished by NH₄Cl loading with food restriction induces soluble CA activity in rabbit renal cortical homogenates. The present study was designed to assess the effect of CMA on the activity of CA isozymes in cortical and outer medullary homogenates, as well as in major proton-secreting segments of the kidney. Segments were microdissected from proximal convoluted tubules (PCT), proximal straight tubules, cortical collecting ducts, and outer medullary collecting ducts (OMCD). Total CA activity was measured by a colorimetric endpoint method, and CA IV activity was assessed from the sodium dodecyl sulfate-resistant hydratase activity. In controls, CA IV activity accounted for 3% of total CA activity in tissue homogenates. CMA induced a threefold increase in CA IV activity in cortical homogenates, in the absence of renal or tubular hypertrophy. In the PCT, CMA induced a 78% increase in total CA activity, which comprised a 178% increase in CA IV activity, and a 58% increase in CA II activity. In the OMCD, CMA induced a 53% increase in total CA (probably CA II) activity. We conclude that CMA induces CA activity in the PCT (CA II and CA IV) and the OMCD (most likely CA II) of adult rabbit kidneys. The induction of CA activity accompanies the increase in urinary acidification observed in CMA.