Parathyroid gland calcium receptor gene expression is not regulated by increased dietary phosphorus in normal and renal failure rats.
The extracellular calcium regulation of parathyroid hormone (PTH) secretion is mediated by a cell surface G-protein-coupled calcium receptor (PCaR). The abnormal calcium sensing in renal failure could be the result of abnormalities of the PCaR. However, PCaR gene expression has been shown to be unaffected by 5/6 nephrectomy in the rat. Whether factors that enhance secondary hyperparathyroidism in renal failure affect the PCaR gene expression is not known. We studied normal rats (sham) (n = 40) and renal failure rats (3/4 nephrectomy) (n = 40). Half of the rats in each group received standard (0.6% calcium, 0.6% phosphorus) and half high phosphorus (0.6% calcium, 1.2% phosphorus) diet. Compared to the standard diet, the high phosphorus diet induced secondary hyperparathyroidism both in sham and in renal failure rats (intact PTH: 22.3 +/- 2.03 vs 54.3 +/- 7.6, P < 0.01, and 26.2 +/- 3.9 vs 178.7 +/- 23.2 pg/ml, P < 0.01, respectively). After the cloning of a rat PCaR cDNA fragment corresponding to the extracellular domain which showed an 89% homology with its bovine counterpart, a probe for Northern blot analysis was obtained. No differences in the PCaR mRNA/18s RNA ratio in high phosphorus compared to the standard diet group were observed, both in sham and in renal failure rats. In conclusion, PCaR gene expression is not involved in the genesis of the secondary hyperparathyroidism induced by a high phosphorus diet. An alternative means of increasing PTH secretion by phosphorus loading could be an alteration of the sensitivity of the PCaR to activation by extracellular calcium.
Hernández
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Unidad de Investigación, Hospital Universitario de Canarias, Universidad de La Laguna, Tenerife, Spain.
Torres
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D008969:Molecular Sequence Data; D010280:Parathyroid Glands / Q000378:metabolism*; D016226:Phosphorus, Dietary / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics*; D051437:Renal Insufficiency / Q000378:metabolism*
D016226:Phosphorus, Dietary; D011956:Receptors, Cell Surface; D002118:Calcium