Blood Ca2+ modulates responsiveness of renal 25(OH)D3-1 alpha-hydroxylase to PTH in rats.
To clarify whether extracellular Ca2+ modulates renal 25-hydroxyvitamin D3 [25(OH)D3]-1 alpha-hydroxylase, thyroparathyroidectomized rats were infused with 15 mM CaCl2, 20 mM EGTA, and/or 2.5 U/h parathyroid hormone (PTH), and blood Ca2+, serum 1,25-dihydroxyvitamin D [1,25(OH)2D], and renal 1 alpha-hydroxylase activity were determined. Rats with CaCl2, EGTA, or PTH infusion (group 1) exhibited low blood Ca2+, serum 1,25(OH)2D, and 1 alpha-hydroxylase activities. Infusion of CaCl2 alone (group 2) caused a significant increase in blood Ca2+ and a reduction in serum 1,25(OH)2D and 1 alpha-hydroxylase compared with group 1. Administration of PTH alone (group 3) markedly elevated blood Ca2+, serum 1,25(OH)2D, and 1 alpha-hydroxylase activity. When EGTA was infused along with PTH (group 4), blood Ca2+ was significantly reduced compared with group 3, and serum 1,25(OH)2D and renal 1 alpha-hydroxylase were further elevated. In contrast, when CaCl2 was infused with PTH (group 5), blood Ca2+ was higher than that in group 3, and serum 1,25(OH)2D and 1 alpha-hydroxylase activities were significantly reduced compared with group 3. No significant difference in serum inorganic phosphate or urinary cAMP excretion was observed by CaCl2 or EGTA infusion in both PTH-treated and nontreated rats. These results demonstrate that extracellular Ca2+ modulates the responsiveness of renal 1 alpha-hydroxylase to PTH as well as the base-line activity of the enzyme in the absence of PTH. These effects of extracellular Ca2+ on renal 1 alpha-hydroxylase may serve to offer an efficient way of regulating 1,25(OH)2D production and serum 1,25(OH)2D concentration by altering the responsiveness of 1 alpha-hydroxylase to PTH and possibly other stimulations depending on the demand for Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Matsumoto
T
T
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Ikeda
K
K
Morita
K
K
Fukumoto
S
S
Takahashi
H
H
Ogata
E
E
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000818:Animals; D001769:Blood; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood* / Q000652:urine; D002122:Calcium Chloride / Q000494:pharmacology; D000242:Cyclic AMP / Q000652:urine; D004533:Egtazic Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010710:Phosphates / Q000097:blood / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000378:metabolism*
D010281:Parathyroid Hormone; D010710:Phosphates; D004533:Egtazic Acid; D000242:Cyclic AMP; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002122:Calcium Chloride; D002118:Calcium