Role of guanine nucleotide binding protein, cytosolic calcium and cAMP in fluoride-induced suppression of PTH secretion.
In the present studies, we used fluoride and pertussis toxin, potent modulators of guanine nucleotide binding proteins (G proteins), to examine the role of G proteins, cytosolic calcium ([Ca]i) and cAMP in the regulation of PTH secretion from dispersed bovine parathyroid cells. NaF suppressed PTH secretion and cAMP content and increased [Ca]i levels in a dose-dependent manner. Prior removal of extracellular calcium with EGTA completely blocked the NaF-induced increase in [Ca]i, but did not prevent the NaF-induced inhibition of PTH secretion and cAMP content. Pretreatment with 10(-5) M verapamil or 10(-4) M diltiazem blocked neither the NaF-induced suppression of PTH secretion and cAMP content nor the increase in [Ca]i. Manganese chloride (10(-4) M) significantly inhibited the NaF-induced increase in [Ca]i, but did not block the NaF-induced suppression of PTH secretion and cAMP content. Pertussis toxin blocked neither the NaF-induced increase in [Ca]i nor suppression of PTH secretion and cAMP content. Our data suggest that (1) NaF might stimulate a calcium channel resulting in the increase in [Ca]i by acting on a G protein in a manner resistant to the inhibition by pertussis toxin; (2) the NaF-induced increase in [Ca]i is not directly linked to the suppression of PTH secretion, and (3) the NaF-induced suppression of PTH secretion might be explained at least in part by the decrease in cell cAMP content.
Sugimoto
T
T
Department of Medicine, Washington University School of Medicine, St. Louis, Mo.
Ritter
C
C
Slatopolsky
E
E
Morrissey
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002712:Chlorides; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D037342:Pertussis Toxin; D015290:Second Messenger Systems; D012969:Sodium Fluoride / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002712:Chlorides; D017895:Manganese Compounds; D010281:Parathyroid Hormone; D010566:Virulence Factors, Bordetella; D008345:Manganese; D012969:Sodium Fluoride; D014700:Verapamil; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D004110:Diltiazem; C025340:manganese chloride; D002118:Calcium