[Apoptosis: a possible mechanism of suppressing parathyroid hyperplasia by calcimimetics]

Clin Calcium. 2005 Sep:15 Suppl 1:56-8; discussion 58-9.
[Article in Japanese]

Abstract

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.

MeSH terms

  • Aniline Compounds / pharmacology*
  • Animals
  • Apoptosis / drug effects*
  • Calcitriol / pharmacology
  • Cells, Cultured
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Hyperparathyroidism, Secondary / metabolism
  • Hyperparathyroidism, Secondary / pathology*
  • Male
  • Parathyroid Glands / cytology*
  • Parathyroid Hormone / metabolism
  • Phenethylamines
  • Propylamines
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Calcium-Sensing / agonists*

Substances

  • Aniline Compounds
  • N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine
  • Parathyroid Hormone
  • Phenethylamines
  • Propylamines
  • Receptors, Calcium-Sensing
  • Calcitriol