Bicarbonate transport by proximal tubules: effect of parathyroid hormone and dibutyryl cyclic AMP

Abstract

Parathyroid hormone (PTH) inhibits HCO3- absorption in the proximal nephron. The mechanisms of this inhibition were not elucidated. The effects of the hormone and dibutyryl cyclic[c]AMP (DBcAMP) on HCO3- transport by rabbit proximal straight tubules were studied in vitro. Bicarbonate was estimated as total CO2 measured by microcalorimetry. With 25 mM HCO3- in both the tubular perfusate and bath, PTH (0.01-1.0 U/ml in the bath) caused the near steady-state total CO2 in the collected fluid to rise in a dose-related fashion from 12.0-22.9 mM. The rates of total CO2 and fluid absorption, JCO2 and Jv, measured at faster perfusion rates, were reduced to 43 and 67% of control values, respectively, by PTH. With 25 mM HCO3- in the bath and 0 mM HCO3- in the perfusate, PTH caused the near steady-state total CO2 in the collected fluid to rise from 6.8-12.1 mM. Similar effects were observed with 10-7 and 10-5 M DBcAMP but not with 10-6 M 5''-AMP. The PTH-induced change in the near steady-state total CO2 concentration in the collected fluid when the perfusate contained 0 mM HCO3- was not associated with a measurable change in the net rate of total CO2 entry into the tubular fluid or in Jv. No effect of PTH was observed in the presence of 10-5 M ouabain. The mechanisms involved in inhibition of HCO3- transport by PTH and DBcAMP in these studies are uncertain and probably complex. The primary process inhibited is probably active lumen-to-bath transport. They may also increase the backleak of HCO3- and/or CO2 from the bath into the tubular lumen.