Regulation of sodium-dependent phosphate transport by parathyroid hormone in opossum kidney cells: adenosine 3',5'-monophosphate-dependent and -independent mechanisms.
The hormonal regulation of Na+-dependent phosphate transport was studied in opossum kidney (OK) cells. PTH caused time- and concentration-dependent decreases in Na+-dependent phosphate transport, with 10 pM PTH-(1-34) producing a 19% decline in phosphate transport. The EC50 for PTH inhibition of phosphate transport was 50 pM. Kinetic analyses of phosphate transport indicated that PTH decreased the maximum velocity without affecting the Km for phosphate. PTH increased cAMP formation with an EC50 of 10 nM. 8-Bromo-cAMP and (Bu)2cAMP also inhibited phosphate transport. Forskolin increased cAMP formation and decreased phosphate transport, whereas the cyclase-inactive forskolin analog 1,9-dideoxyforskolin also inhibited phosphate transport. The PTH analog [8,18-norleucine,34-tyrosinamide]PTH-(3-34) reduced phosphate transport at concentrations from 10 nM to 30 microM, but did not increase cAMP formation at concentrations up to 10 microM. The adenylate cyclase inhibitor 2',5'-dideoxyadenosine produced concentration-dependent decreases in PTH-stimulated cAMP formation, but did not influence PTH inhibition of Na+-dependent phosphate transport. Vasoactive intestinal polypeptide and prostaglandin E1 increased cAMP formation in OK cells, but were weak inhibitors of phosphate transport. This study suggests that cAMP may not be the only transmembrane signaling mechanism involved in the regulation of Na+-dependent phosphate transport by PTH-(1-34) in OK cells.
Cole
J A
JA
Department of Pharmacology, University of Missouri School of Medicine, Columbia 65212.
Forte
L R
LR
Eber
S
S
Thorne
P K
PK
Poelling
R E
RE
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis / Q000494:pharmacology*; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D009893:Opossums / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology*; D019379:Teriparatide; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D003839:Deoxyadenosines; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010710:Phosphates; D019379:Teriparatide; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014660:Vasoactive Intestinal Peptide; D016048:Dideoxyadenosine; C031617:parathyroid hormone (3-34); D003994:Bucladesine; C021008:2',5'-dideoxyadenosine; D012964:Sodium; D000242:Cyclic AMP; D000527:Alprostadil