The calcimimetic compound NPS R-568 suppresses parathyroid cell proliferation in rats with renal insufficiency - Control of parathyroid cell growth via a calcium receptor

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 8-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)(2)D-3 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.