Mechanisms of inhibition of proximal acidification by PTH

The parathyroid hormone (PTH) effects on luminal Na-H exchange and basolateral Na-HCO3 cotransport were examined in isolated perfused rabbit proximal convoluted tubules. Lumen pH (pHi) and cell pH (pHi) were measured by a fluorescent technique using 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). The time course of the PTH effect on proximal acidification was first determined by continuous monitoring of pHi in a stop-flow condition. PTH 10(-8) M added to the bath promptly inhibited the acid pHl generation. Adenosine 3',5'-cyclic monophosphate (cAMP) (10(-4) M) added to the bath mimicked the PTH effect. Luminal Na-H exchange was assayed by monitoring changes in pHi (dpHi/dt) in response to luminal Na+ removal in HCO3- free condition. The addition of PTH or cAMP for 5 min decreased dpHi/dt by 30 and 37%, respectively. Basolateral Na-HCO3 cotransport was assayed by measuring dpHi/dt caused by bath Na+ removal. The addition of PTH or cAMP for 5 min did not change the dpHi/dt. PTH also did not alter the dpHi/dt induced by reducing the bath HCO3- from 25 to 5 mM. The addition of PTH or cAMP to the bath slightly reduced pHi by 0.05. These results suggest that 1) PTH inhibits proximal acidification very rapidly and the effect reached a maximum within 10 min, 2) PTH rapidly inhibits luminal Na-H exchange but not basolateral Na-HCO3 cotransport in a short period, and 3) this effect is at least partly mediated by cAMP-dependent mechanisms.