Parathyroid hormone action on phosphate transport is inhibited by high osmolality.
Parathyroid hormone (PTH) produces rapid inhibition of Na(+)-phosphate cotransport, characterized by a decreased maximal rate of transport, and the inhibition is independent of de novo protein synthesis. The present study determined whether the action of PTH on Na(+)-phosphate cotransport is mediated, at least in part, by rapid endocytic internalization of Na(+)-phosphate cotransporters present in the plasma membrane. Horseradish peroxidase, a fluid-phase marker, was used to demonstrate the presence of endocytosis in opossum kidney (OK) epithelial cells in monolayer culture. An increase in medium osmolality to 500 mosmol/kgH2O, by addition of sucrose, produced 80% inhibition of endocytosis within 1 h. The inhibition was reversed on returning the cells to normal medium. Incubation of OK cell monolayers with PTH (10(-8) M) for 3 h at normal osmolality (281 mosmol/kgH2O) inhibited Na(+)-phosphate cotransport (4 min uptakes) by 56-67%. In hyperosmolar medium (513 mosmol/kgH2O), when endocytosis was inhibited, PTH inhibited Na(+)-phosphate cotransport by only 25-39%, a change that was significantly different from the inhibition in normal medium. Hyperosomolality had no effect on PTH inhibition of Na(+)-H+ exchange or on PTH stimulation of intracellular adenosine 3',5'-cyclic monophosphate. We conclude that the full inhibitory action of PTH on Na(+)-phosphate cotransport may require an intact endocytic mechanism.
Kempson
S A
SA
Physiology Institute, University of Zurich, Switzerland.
Helmle
C
C
Abraham
M I
MI
Murer
H
H
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D003470:Culture Media; D004705:Endocytosis; D006735:Horseradish Peroxidase; D007668:Kidney / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D009994:Osmolar Concentration; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D003470:Culture Media; D010281:Parathyroid Hormone; D010710:Phosphates; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D006735:Horseradish Peroxidase