Effect of prostaglandin F2 alpha on human parathyroid adenomas: evidence for uncoupling of parathyroid hormone secretion and cAMP accumulation.
Human parathyroid adenomas are aberrantly regulated by extracellular calcium. We tested pertussis toxin, which ADP-ribosylates and inactivates several guanine nucleotide regulatory proteins, to test the role of these proteins in the secretory control of adenomatous parathyroid tissue. Pertussis toxin did not affect basal cAMP accumulation in 12 adenomas and enhanced parathyroid hormone (PTH) release in 6 of 10 adenomas. Prostaglandin F2 alpha (PGF2 alpha) inhibited cAMP in three of six adenomas, and pertussis toxin pretreatment did not affect this result. PTH release in 7 of 10 adenomas was inhibited by PGF2 alpha, and pertussis toxin did not significantly alter PTH release. Pertussis toxin catalyzed ADP-ribosylation of a 40-kDa protein in all adenomas tested (n = 8). We conclude that cAMP accumulation was not affected by pertussis toxin but that in 6 of 10 adenomas, the toxin enhanced PTH release. We suggest that cAMP accumulation and PTH release may be uncoupled from negative control by inhibitory ligands in adenomatous tissue or that the G-proteins involved do not couple to regulatory receptors or to effector.
Fitzpatrick
L A
LA
Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
Norton
J
J
Martin
C
C
Sharp
M
M
Aurbach
G D
GD
D000236:Adenoma / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000378:metabolism*; D010282:Parathyroid Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D037342:Pertussis Toxin; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010281:Parathyroid Hormone; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D015237:Dinoprost; D000242:Cyclic AMP; D037342:Pertussis Toxin; D007545:Isoproterenol; D004837:Epinephrine