Activation of calcium-sensing receptor accelerates apoptosis in hyperplastic parathyroid cells.
Calcimimetic compounds inhibit not only parathyroid hormone (PTH) synthesis and secretion, but also parathyroid cell proliferation. The aim of this investigation is to examine the effect of the calcimimetic compound NPS R-568 (R-568) on parathyroid cell death in uremic rats. Hyperplastic parathyroid glands were obtained from uremic rats (subtotal nephrectomy and high-phosphorus diet), and incubated in the media only or the media which contained high concentration of R-568 (10(-4)M), or 10% cyclodextrin, for 6h. R-568 treatment significantly suppressed medium PTH concentration compared with that of the other two groups. R-568 treatment not only increased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay-positive cells, but also induced the morphologic changes of cell death determined by light or electron microscopy. These results suggest that CaR activation by R-568 accelerates parathyroid cell death, probably through an apoptotic mechanism in uremic rats in vitro.
Mizobuchi
Masahide
M
Department of Nephrology, School of Medicine, Showa University, Tokyo, Japan.
Ogata
Hiroaki
H
Department of Internal Medicine, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-chuo, Tsuzuki, Yokohama 224-8503, Japan. Electronic address: ogatah@med.showa-u.ac.jp.
Hatamura
Ikuji
I
First Department of Pathology, Wakayama Medical University, Wakayama, Japan.
Saji
Fumie
F
Division of Nephrology and Blood Purification Medicine, Wakayama Medical University, Wakayama, Japan.
Koiwa
Fumihiko
F
Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
Kinugasa
Eriko
E
Department of Internal Medicine, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-chuo, Tsuzuki, Yokohama 224-8503, Japan.
Koshikawa
Shozo
S
Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
Akizawa
Tadao
T
Department of Nephrology, School of Medicine, Showa University, Tokyo, Japan.
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D003505:Cyclodextrins / Q000378:metabolism; D006965:Hyperplasia / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D008297:Male; D008854:Microscopy, Electron; D008954:Models, Biological; D010280:Parathyroid Glands / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D010627:Phenethylamines; D011437:Propylamines; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism
D000814:Aniline Compounds; D003505:Cyclodextrins; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010627:Phenethylamines; D011437:Propylamines; D044169:Receptors, Calcium-Sensing