Parathyroid hormone stimulation of renal phosphoinositide metabolism is a cyclic nucleotide-independent effect

The effects of parathyroid hormone (PTH) and cyclic nucleotides on renal phosphoinositide metabolism were studied using cortical tubules isolated from dog kidneys. PTH stimulated the initial rates of ³²P_i incorporation into phosphatidylinositol 4'5'-diphosphate, phosphatidylinositol 4'-monophosphate, phosphatidylinositol and phosphatidic acid. PTH also caused a 45-55% increase in the actual tissue levels of these phospholipids by 5 min of incubation. By 30 min of incubation, the levels of ³²_i incorporated were similar in PTH and control flasks, but the actual levels of the phosphoinositides remained elevated, indicating stimulation of their turnover. Additional evidence of increased turnover of phosphatidylinositol was obtained from tubules pre-incubated with myo-[2-³H] inositol. PTH stimulated a rapid short-lived decrement in [³H]phosphati-dylinositol while total phosphatidylinositol levels increased, indicating increased turnover rates of phosphati-dylinositol. In tubules pre-incubated with [¹⁴C]arachidonic acid, PTH increased the initial rates of [¹⁴C]di-acylglycerol production and decreased release of [¹⁴C]arachidonic acid, indicating utilization of diacylglycerol produced during turnover for resynthesis of phosphatidic acid and phosphoinositides. Cyclic nucleotides and phosphodiesterase inhibition failed to reproduce the effect of PTH on phosphoinositide metabolism. These studies indicate that PTH stimulates renal phosphoinositide metabolism through a mechanism independent of cAMP which results in a net synthesis of the phosphoinositides.