Different mechanisms of action of acetazolamide and parathyroid hormone on proximal tubular absorption of fluid and 5,5-dimethyl-2,4- oxazolidinedione

YL Chan

The effects of acetazolamide (Diamox), parathyroid hormone (PTH) and dibutyrylcyclic-adenosine 3':5'-monophosphate (db-cAMP) on fluid and 5,5-dimethyl-2,4-oxazolidinedione (DMO) absorption in the rat proximal convoluted tubule were studied by using microperfusion methods. The rate of tubular absorption of DMO was used to estimate the rate of hydrogen ion secretion. When the tubular and the peritubular capillaries were perfused simultaneously with bicarbonate-free Ringer's solution containing DMO, the rate of DMO absorption (JDMO) was 140 +/- 15.7 pmol/min . mm, a value comparable to the rate of absorption of bicarbonate and glycodiazine, and net fluid absorption (JV) was 2.20 +/- 0.19 nl/min . mm. Administration of PTH (10(-6) M) to the capillary perfusate caused a decrease of JDMO by 23% and a decrease of JV by 28%. Similar results were observed when db-cAMP (10(-4) M) was administered to the luminal perfusate. Addition of acetazolamide (10(-4) M) to the luminal perfusate caused a decrease of JDMO by 66% and a decrease of JV by 45%. The effect of either PTH or db-cAMP was additive to the maximal effect of acetazolamide. However, the effect of PTH was not additive to the effect of db-cAMP. Thus, the results suggest that PTH and acetazolamide have different mechanisms of action on fluid and DMO absorption by proximal tubule and that cAMP mediates the effect of PTH.

Volume 215, Issue 3, pp. 557-562, 12/01/1980
Copyright © 1980 by American Society for Pharmacology and Experimental Therapeutics

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