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Am J Physiol Endocrinol Metab 253: E503-E507, 1987;
0193-1849/87 $5.00
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AJP - Endocrinology and Metabolism, Vol 253, Issue 5 E503-E507, Copyright © 1987 by American Physiological Society

ARTICLES

Blood Ca2+ modulates responsiveness of renal 25(OH)D3-1 alpha-hydroxylase to PTH in rats

T. Matsumoto, K. Ikeda, K. Morita, S. Fukumoto, H. Takahashi and E. Ogata
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.

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)


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