Parathyroid hormone inhibition of Na+/phosphate cotransport in OK cells: requirement of protein kinase C-dependent pathway.
Parathyroid hormone (PTH) inhibits sodium/phosphate (Na+/Pi) cotransport across the apical membrane of opossum kidney (OK) cells principally through two pathways. First, cAMP stimulation and activation of protein kinase A; second, diacylglycerol release and stimulation of protein kinase C. Studies were designed to determine the importance of these regulatory cascades. Down-regulation of protein kinase C with prolonged phorbol ester (12-O-tetradecanoylphorbol 13-acetate (TPA] treatment leads to a refractory state in which the cells do not respond to PTH (10(-8) M), cAMP (10(-4) M) or rechallenge of TPA (200 nM) even though Na+/Pi cotransport is similar to control cells (8.1 +/- 0.1 nmol.mg-1 protein.5 min-1). Staurosporine, an inhibitor of protein kinase C, resulted in the complete inhibition of PTH, cAMP and TPA action in a dose-dependent manner. PTH, cAMP and TPA were additive below maximal concentrations, but had no further effect at maximal agonist concentrations. These results suggest that protein kinase C activity is important in PTH-mediated inhibition of Na+/phosphate cotransport in OK cells.
Quamme
G
G
Institute of Physiology, University of Zurich, Switzerland.
Pfeilschifter
J
J
Murer
H
H
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D009893:Opossums; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D019311:Staurosporine; D027981:Symporters; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D002352:Carrier Proteins; D004075:Diglycerides; D010281:Parathyroid Hormone; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D005576:Colforsin; D000242:Cyclic AMP; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate