title: The calcimimetic compound NPS R-568 suppresses parathyroid cell proliferation in rats with renal insufficiency. Control of parathyroid cell growth via a calcium receptor.
abstract: Parathyroid (PT) cell hyperplasia is a common consequence of chronic renal insufficiency (CRI). NPS R-568 is a phenylalkylamine compound that acts as an agonist (calcimimetic) at the cell surface calcium receptor (CaR). To test the hypothesis that the CaR plays a role in PT hyperplasia in CRI, we tested the effect of NPS R-568 on PT cell proliferation in rats with renal insufficiency. Rats were subjected to 5/6 nephrectomy and then infused intraperitoneally with 5-bromodeoxyuridine (BrdU) to label S-phase cells. Two groups of nephrectomized rats received NPS R-568 by gavage twice daily for 4 d (1.5 and 15 mg/kg body wt). On day 5, the number of BrdU-positive PT cells of vehicle-treated nephrectomized rats was 2.6-fold greater than that of the sham-operated control. Low and high doses of NPS R-568 reduced the number of BrdU-positive PT cells by 20 and 50%, respectively. No changes in staining, however, were observed in ileal epithelial cells (CaR-negative) or in thyroidal C-cells (CaR-positive). Furthermore, the effect of NPS R-568 could not be explained by changes in serum 1,25(OH)2D3 or phosphorus. These results indicate that NPS R-568 suppresses PT cell proliferation in rats with renal insufficiency, and lend support to the linkage between the CaR and PT hyperplasia in CRI.
authors.affiliation: Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Takasaki-shi, Gunma 370-12, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Wada
authors.forename: Y
authors.initials: Y
authors.lastname: Furuya
authors.forename: J
authors.initials: J
authors.lastname: Sakiyama
authors.forename: N
authors.initials: N
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Miyata
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: N
authors.initials: N
authors.lastname: Nagano
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D002117:Calcitriol / Q000378:metabolism; D002118:Calcium / Q000819:agonists* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D006131:Growth Inhibitors / Q000494:pharmacology*; D008297:Male; D010280:Parathyroid Glands / Q000187:drug effects* / Q000473:pathology; D010281:Parathyroid Hormone / Q000378:metabolism; D010627:Phenethylamines; D011437:Propylamines; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000378:metabolism / Q000473:pathology*
chemical_list: D000814:Aniline Compounds; D006131:Growth Inhibitors; C107873:N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine; D010281:Parathyroid Hormone; D010627:Phenethylamines; D011437:Propylamines; D003404:Creatinine; D002117:Calcitriol; D002118:Calcium