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.
Sasaki
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S
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Marumo
F
F
D000818:Animals; D001639:Bicarbonates / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers; D013997:Time Factors
D001639:Bicarbonates; D002352:Carrier Proteins; D010281:Parathyroid Hormone; D017923:Sodium-Hydrogen Exchangers; D000242:Cyclic AMP