[Apoptosis: a possible mechanism of suppressing parathyroid hyperplasia by calcimimetics].
The mechanism through which calcimimetic compounds suppress parathyroid cell growth has not been fully elucidated. We investigated the effect of the calcimimetic compound (NPS R-568:R568) on the parathyroid cell growth in vitro. Whole parathyroid glands of subtotally nephrectomized rats fed high phosphorus diet for 8 weeks were used in this study. Fresh rat parathyroid glands were incubated in a media (phosphorus concentration is 1.0 mM and calcium is 1.25 mM) with R-568 (10-4 M) or calcitriol (10-7 M) or vehicle for 6 hours. Medium PTH level was significantly decreased in both R568-treated group and calcitriol-treated group compared with either vehicle-treated group, or no-treated group. While TUNEL-positive cells were similar in calcitriol-treated group compared with both vehicle-treated and no-treated groups, they were significantly increased in R568-treated group compared with other three groups. These results suggest that calcimimetic compounds, NPS R-568 reduces PTH secretion and induces apoptosis of hyperfunctional parathyroid cell in vitro.
Mizobuchi
Masahide
M
Nephrology and Blood Purification Medicine, Wakayama Medical University.
Saji
Fumie
F
Shiizaki
Kazuhiro
K
Sato
Toshihiro
T
Shibata
Maki
M
Negi
Shigeo
S
Akizawa
Tadao
T
Hatamura
Ikuji
I
Ogata
Hiroaki
H
Kinugasa
Eriko
E
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002117:Calcitriol / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010280:Parathyroid Glands / Q000166:cytology*; D010281:Parathyroid Hormone / Q000378:metabolism; D010627:Phenethylamines; D011437:Propylamines; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000819:agonists*
D000814:Aniline Compounds; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010281:Parathyroid Hormone; D010627:Phenethylamines; D011437:Propylamines; D044169:Receptors, Calcium-Sensing; D002117:Calcitriol