Modulation of the Ca2+-sensing function of parathyroid cells in vitro and in hyperparathyroidism.
When raising the extracellular Ca2+ concentration stepwise from 0.5 to 3.0 mM, bovine parathyroid cells reacted with initial transient and sustained elevations of the cytoplasmic Ca2+ concentration (Ca2+i), as well as more than 50% inhibition of parathyroid hormone (PTH) release. Human parathyroid adenoma cells and bovine cells cultured for 1 day or exposed to a low concentration of a monoclonal antiparathyroid antibody exhibited right-shifted dependencies of PTH release and Ca2+i on extracellular Ca2+ and reduced Ca2+i transients. The protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA) further right-shifted the dose response relationship for Ca2+ regulated Ca2+i of the adenoma cells, whereas the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) tended to normalize it, without affecting Ca2+i of normal bovine cells. In cells from an oxyphil adenoma and a parathyroid carcinoma as well as in bovine cells cultured 4 days or exposed to a high concentration of the antiparathyroid antibody, there were no Ca2+i transients, very small increases in steady-state Ca2+i and nonsuppressible PTH release. The results suggest that reduced availability of a putative Ca2+-receptor and increased protein kinase C activity may be important factors in the decreased Ca2+ sensitivity of abnormal parathyroid cells.
Nygren
P
P
Department of Medical Cell Biology, University of Uppsala, Sweden.
Gylfe
E
E
Larsson
R
R
Johansson
H
H
Juhlin
C
C
Klareskoq
L
L
Akerström
G
G
Rastad
J
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000236:Adenoma / Q000150:complications; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002277:Carcinoma / Q000150:complications / Q000378:metabolism; D002417:Cattle; D005110:Extracellular Space / Q000032:analysis; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D010280:Parathyroid Glands / Q000276:immunology / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism; D010282:Parathyroid Neoplasms / Q000150:complications; D010879:Piperazines / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007546:Isoquinolines; D010281:Parathyroid Hormone; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium