CALCIUM RECEPTOR MESSENGER-RIBONUCLEIC-ACID LEVELS IN THE PARATHYROID-GLANDS AND KIDNEY OF VITAMIN-D-DEFICIENT RATS ARE NOT REGULATED BY PLASMA CALCIUM OR 1,25-DIHYDROXYVITAMIN-D-3

The level of extracellular ionized calcium ([Ca2+](0)) is the primary physiological regulator of PTH secretion. Complementary DNAs encoding the calcium receptor (CaR) protein that mediates this response have be en cloned from bovine and human parathyroid glands. This protein is a seven-transmembrane, G-protein-coupled receptor linked to the mobiliza tion of intracellular Ca2+ in response to increases in [Ca2+](0). More recently, a rat kidney CaR has been cloned and shown to be 92% identi cal at the amino acid level to the bovine parathyroid CaR. Homologous or heterologous regulation of the expression and/or function of a vari ety of G-protein-coupled receptors has been documented in numerous cel l types. Therefore, we determined whether [Ca2+](0) and 1,25-dihydroxy vitamin D-3 [1,25-(OH)(2)D-3], major regulators of PTH synthesis and s ecretion, affect CaR gene expression in parathyroid gland and kidney i n rats. CaR messenger RNA (mRNA) levels were quantified in pairs of pa rathyroid glands and single kidneys from individual animals using a so lution hybridization assay. The effects of Ca2+ and 1,25-(OH)(2)D-3 on CaR gene expression were assessed independently in vitamin D-deficien t (-D) rats. A wide range of plasma Ca2+ levels (0.7-1.9 mM) was produ ced by supplementing -D diets with varying amounts of calcium and by i nfusing CaCl2 iv for 7 days using osmotic minipumps. There was no corr elation between plasma Ca2+ levels and steady state CaR mRNA levels in parathyroid gland (r = -0.18) or kidney (r = 0.25). In another group of -D rats, 1,25-(OH)(2)D-3 was infused sc at 25 and 275 ng/kg.day for 10-12 days. Dietary calcium was adjusted to maintain normocalcemia in some of the groups. No effect of 1,25-(OH)(2)D-3 administration on Ca R mRNA levels occurred in parathyroid glands or kidney regardless of t he resultant plasma Ca2+ or 1,25-(OH)(2)D-3 levels. In conclusion, nei ther parathyroid gland nor kidney CaR mRNA levels are regulated by pla sma Ca2+ and 1,25-(OH)(2)D-3 levels in the experimental models examine d here.