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 D3.
The level of extracellular ionized calcium ([Ca2+]o) is the primary physiological regulator of PTH secretion. Complementary DNAs encoding the calcium receptor (CaR) protein that mediates this response have been cloned from bovine and human parathyroid glands. This protein is a seven-transmembrane, G-protein-coupled receptor linked to the mobilization of intracellular Ca2+ in response to increases in [Ca2+]o. More recently, a rat kidney CaR has been cloned and shown to be 92% identical at the amino acid level to the bovine parathyroid CaR. Homologous or heterologous regulation of the expression and/or function of a variety of G-protein-coupled receptors has been documented in numerous cell types. Therefore, we determined whether [Ca2+]o and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], major regulators of PTH synthesis and secretion, affect CaR gene expression in parathyroid gland and kidney in rats. CaR messenger RNA (mRNA) levels were quantified in pairs of parathyroid glands and single kidneys from individual animals using a solution hybridization assay. The effects of Ca2+ and 1,25-(OH)2D3 on CaR gene expression were assessed independently in vitamin D-deficient (-D) rats. A wide range of plasma Ca2+ levels (0.7-1.9 mM) was produced by supplementing -D diets with varying amounts of calcium and by infusing CaCl2 i.v. for 7 days using osmotic minipumps. There was no correlation 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)2D3 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)2D3 administration on CaR mRNA levels occurred in parathyroid glands or kidney regardless of the resultant plasma Ca2+ or 1,25-(OH)2D3 levels. In conclusion, neither parathyroid gland nor kidney CaR mRNA levels are regulated by plasma Ca2+ and 1,25-(OH)2D3 levels in the experimental models examined here.
Department of Molecular Biology, NPS Pharmaceuticals, Inc., Salt Lake City, Utah 84108, USA.
K V
KV
Rogers
C K
CK
Dunn
R L
RL
Conklin
S
S
Hadfield
B A
BA
Petty
E M
EM
Brown
S C
SC
Hebert
E F
EF
Nemeth
J
J
Fox
D000818:Animals; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000008:administration & dosage* / Q000097:blood; D002136:Calcium, Dietary; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002417:Cattle; D002762:Cholecalciferol / Q000008:administration & dosage / Q000097:blood / Q000172:deficiency*; D004032:Diet; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010280:Parathyroid Glands / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014808:Vitamin D Deficiency / Q000378:metabolism*
D002136:Calcium, Dietary; D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; D002762:Cholecalciferol; D002117:Calcitriol; D002118:Calcium