Prostaglandin F2 alpha and alpha-adrenergic agonists regulate parathyroid cell function via the inhibitory guanine nucleotide regulatory protein.
Prostaglandin F2 alpha (PGF2 alpha) and alpha-adrenergic agonists inhibit cAMP production and PTH secretion in dispersed bovine parathyroid cells. We have tested the mechanism of these effects utilizing pertussis toxin which catalyzes ADP ribosylation and inactivation of the inhibitory adenylate cyclase coupling protein Ni. Dispersed bovine parathyroid cells treated with or without 0.5 micrograms/ml pertussis toxin were tested with stimulatory (epinephrine, isoproterenol) or inhibitory (PGF2 alpha) agonists for responses in cAMP accumulation (5-min incubation) or PTH (90-min incubation) release. Pertussis toxin produced an enhanced response to epinephrine (a mixed alpha-adrenergic and beta-adrenergic agonist) in cAMP production and in PTH secretion. PGF2 alpha inhibited intracellular cAMP by 40% and PTH secretion by 35%. Pertussis toxin treatment of bovine parathyroid cells reduced the PGF2 alpha inhibition. We conclude that: 1) inhibition of PTH release by PGF2 alpha and alpha-adrenergic agonists parallels inhibition of cAMP production; 2) pertussis toxin blocks the inhibitory actions of PGF2 alpha and alpha-adrenergic agents on cAMP accumulation and PTH secretion; 3) the inhibitory coupling protein Ni mediates the inhibitory effects of these agents.
Fitzpatrick
L A
LA
Brandi
M L
ML
Aurbach
G D
GD
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D000242:Cyclic AMP / Q000096:biosynthesis; D015237:Dinoprost; D004837:Epinephrine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism; D037342:Pertussis Toxin; D011460:Prostaglandins F / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists; D010281:Parathyroid Hormone; D011460:Prostaglandins F; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D015237:Dinoprost; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D004837:Epinephrine