Stimulation of transient elevations in cytosolic Ca2+ is related to inhibition of Pi transport in OK cells.
Stimulation of changes in cytosolic free calcium by parathyroid hormone was determined in three opossum kidney (OK) cell types, OK wild-type, OKP clone, and OKH clone. All three types of OK cells express parathyroid hormone (PTH)-sensitive adenylate cyclase and adenosine 3',5'-cyclic monophosphate (cAMP) production. However, only the OK wild-type and the OKP clone respond to PTH with inhibition of sodium-dependent Pi transport and transient increase in cytosolic calcium. Characterization of the increases in cytosolic calcium in the wild-type and OKP clones revealed they were due in part to stimulation of Ca2+ release from intracellular stores, probably by inositol 1,4,5-trisphosphate (IP3), which was stimulated by PTH. PTH-stimulated Ca2+ transients were also inhibited by protein kinase C activation. These data are compatible with PTH receptor-mediated phospholipase C activation and its feedback inhibition by protein kinase C. The OKH cells demonstrated a slow increase in cytosolic calcium when stimulated by cyclic nucleotides but no evidence for PTH stimulation of Ca2+ release from intracellular stores. Thus the absence of an inhibitory response of sodium-dependent Pi transport to PTH in the OKH cells is associated with the absence of the rapid transient elevations of cytosolic Ca2+ such as those produced by IP3 production. These data suggest an important cooperative role for cAMP and the phospholipase C-stimulated Ca2(+)-protein kinase C message system in the regulation of Pi transport.
Department of Medicine, Jewish Hospital at Washington University, St. Louis 63110.
A
A
Miyauchi
V
V
Dobre
M
M
Rickmeyer
J
J
Cole
L
L
Forte
K A
KA
Hruska
D037361:Adenylate Cyclase Toxin; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism* / Q000502:physiology; D004594:Electrophysiology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D009893:Opossums; D009994:Osmolar Concentration; D010281:Parathyroid Hormone / Q000494:pharmacology; D010710:Phosphates / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D009712:Nucleotides, Cyclic; D010281:Parathyroid Hormone; D010710:Phosphates; D010566:Virulence Factors, Bordetella; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium