Parathyroid hormone stimulates phosphate efflux through an apparently adenosine 3',5'-monophosphate-independent...

The effects of PTH on phosphate fluxes and cAMP and protein secretion in rat parotid cell aggregates were studied. PTH-(1-34) as well as PTH-(1-84) stimulated phosphate efflux in a dose-dependent [5 X 10(-7) to 7 X 10(-6) M for human (h) PTH-(1-34), 2 X 10(-7) to 5 X 10(-6) M for bovine (b) PTH-(1-34), and 3.8-114 U/ml for bPTH-(1-84)] and time-dependent [detectable by 15-30 min after incubation with N-terminal PTH and 30-45 min after incubation with bPTH-(1-84)] manner. The effect of PTH on phosphate efflux was saturable, with maximal stimulation at 10(-6) M above for N-terminal PTH and at 57.8 U/ml and above for bPTH-(1-84). Half-maximal stimulation of phosphate efflux by hPTH-(1-34), bPTH-(1-34), and bPTH-(1-84) was achieved at 5.7 X 10(-7) M, 10(-7) M, and 40 U/ml, respectively. Neither bPTH-(1-34) nor bPTH-(1-84) had any effect on phosphate uptake by parotid cell aggregates at the concentrations examined. bPTH-(1-34) and bPTH-(1-84) also stimulated amylase secretion, with a significant increase in cAMP production (70-90% over basal). However, (BU)2cAMP did not stimulate phosphate efflux. Isoproterenol (10(-5) M) markedly stimulated cAMP production and amylase secretion without causing a significant increase in phosphate efflux. Oxidized bPTH-(1-84) and the C-terminal fragment of hPTH had no stimulating effect on phosphate efflux. The present results suggest, therefore, that PTH may play an important role in regulating rat parotid cell phosphate metabolism through an apparently cAMP-independent process.