PARATHYROID-HORMONE STIMULATES ECTO-5' NUCLEOTIDASE ACTIVITY IN RENALEPITHELIAL-CELLS - ROLE OF PROTEIN-KINASE-C

PTH-induced phosphaturia is exerted in part by cAMP added to the renal tubular lumen under the influence of the hormone. Modulation of renal phosphate transport by luminal cAMP requires degradation of the nucle otide into adenosine by brush-border membrane ectoenzymes, among them ecto-5'-nucleotidase (5'-NU). Hormonal modulation of 5'-NU activity wa s evaluated in cultured opossum kidney cells. PTH (1-100 nM) stimulate d 5'-NU in a time-, concentration-, and protein synthesis-dependent ma nner. The effect of PTH-(1-34) was mimicked by PTH-(3-34), which does not activates adenylate cyclase, and by phorbol 12-myristate 13-acetat e (PMA), but not by forskolin or (Bu)(2)cAMP. Down-regulation or pharm acological inhibition of protein kinase-C (PKC) abolished the effect o f PTH fragments and PMA. PTH fragments increased intracellular Ca2+ an d translocated PKC activity to the membrane. PTH or PMA did not affect 5'-NU messenger RNA content. Inhibition of sodium-phosphate cotranspo rt by extracellular cAMP was decreased by 5'-NU inhibition and was mag nified by PTH. These results indicate that 1) PTH stimulates 5'-NU act ivity in renal proximal tubular cells in a manner involving PKC activa tion and de novo protein synthesis; and 2) this effect participates in PTH modulation of renal phosphate transport.