Parathyroid hormone inhibition of Na+/phosphate cotransport in OK cells: generation of second messengers in the regulatory cascade.
Dose-dependent inhibition of Na/phosphate cotransport by parathyroid hormone (PTH) was correlated with the generation of hormone-mediated second messengers, cAMP, 1,2-diacylglycerol and inositol 1,4,5 trisphosphate in an established epithelial cell line (opossum kidney (OK) cells). PTH results in a dose-dependent decline in Na/phosphate cotransport with a half-maximal response at about 10(-11) M. This hormone concentration is commensurate with the levels required to increase 1,2-diacylglycerol and inositol 1,4,5-trisphosphate concentrations by about half maximal but not with those needed for cAMP generation (10(-9) to 10(-8) M PTH). Accordingly, activation of phospholipase C may be physiologically more important than stimulation of adenylate cyclase at normal PTH levels.
Quamme
G
G
Department of Medicine, University of British Columbia, Vancouver, Canada.
Pfeilschifter
J
J
Murer
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D009893:Opossums; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism*; D015290:Second Messenger Systems; D012964:Sodium / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
C011439:1,2-diacylglycerol; D004075:Diglycerides; D007295:Inositol Phosphates; D010281:Parathyroid Hormone; D010710:Phosphates; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015544:Inositol 1,4,5-Trisphosphate; D012964:Sodium; D000242:Cyclic AMP; D010738:Type C Phospholipases; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine