title: Activation of calcium-sensing receptor accelerates apoptosis in hyperplastic parathyroid cells.
abstract: 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.
authors: Department of Nephrology, School of Medicine, Showa University, Tokyo, Japan.
authors: Masahide
authors: M
authors: Mizobuchi
authors: 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.
authors: Hiroaki
authors: H
authors: Ogata
authors: First Department of Pathology, Wakayama Medical University, Wakayama, Japan.
authors: Ikuji
authors: I
authors: Hatamura
authors: Division of Nephrology and Blood Purification Medicine, Wakayama Medical University, Wakayama, Japan.
authors: Fumie
authors: F
authors: Saji
authors: Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors: Fumihiko
authors: F
authors: Koiwa
authors: Department of Internal Medicine, Showa University Northern Yokohama Hospital, 35-1, Chigasaki-chuo, Tsuzuki, Yokohama 224-8503, Japan.
authors: Eriko
authors: E
authors: Kinugasa
authors: Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan.
authors: Shozo
authors: S
authors: Koshikawa
authors: Department of Nephrology, School of Medicine, Showa University, Tokyo, Japan.
authors: Tadao
authors: T
authors: Akizawa
mesh_terms: 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
chemical_list: D000814:Aniline Compounds; D003505:Cyclodextrins; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010627:Phenethylamines; D011437:Propylamines; D044169:Receptors, Calcium-Sensing