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| SUPPRESSION OF PTH AND DECREASED ACTION ON BONE ARE PARTIALLY RESPONSIBLE FOR THE LOW CALCEMIC ACTIVITY OF 22-OXACALCITRIOL RELATIVE TO 1,25-(OH)2D3 |
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| Author(s): FINCH JL, BROWN AJ, MORI T, NISHII Y, SLATOPOLSKY E |
| Source: JOURNAL OF BONE AND MINERAL RESEARCH Volume: 7 Issue: 7 Pages: 835-839 Published: JUL 1992 |
| Times Cited: 13 References: 29 |
| Abstract: We previously showed that OCT, an analog of 1,25-(OH)2D3 with little calcemic activity, can decrease PTH mRNA levels in normal rats and inhibit PTH secretion in cultured bovine parathyroid cells with the same potency as 1,25-(OH)2D3 and that in normal rats fed a normal calcium diet, administration of OCT (500 ng) for 5 days did not increase plasma Ca. Thus, to determine if PTH suppression by OCT contributes to its lack of calcemic activity and to further characterize the effects of OCT on Ca metabolism, we performed several studies in parathyroidectomized (PTX) rats. PTX rats, maintained on a normal diet (0.9% Ca), received daily injections of vehicle, 1,25-(OH)2D3 (200 ng/day), or OCT (200 ng/day) for 6 days. Plasma Ca was measured daily. Plasma Ca in control rats stayed between 6.60 and 7.40 mg/dl, whereas Ca increased to 12.9 +/- 0.42 mg/dl in 1,25-(OH)2D3-treated rats and to 9.53 +/- 0.35 mg/dl in OCT-treated rats after 6 days. With a Ca-deficient diet, control rats maintained a plasma Ca between 4.25 and 4.60 mg/dl, but Ca increased to 13.7 +/- 0.24 mg/dl with 1,25-(OH)2D, and to 7.29 +/- 0.17 mg/dl with OCT. Since the elevation in Ca by OCT was similar with both diets, OCT appears to act primarily on bone. PTX rats were infused with PTH (1.84-mu-g/kg/day) vis an Alzet pump to achieve normal plasma Ca and then treated daily with either vehicle or OCT (200 ng/day). After 6 days, OCT increased serum Ca to 10.7 +/- 0.21 mg/dl over a control value of 8.58 +/- 0.29 mg/dl. Thus, even when normocalcemic conditions were maintained with a nonsuppressible source of PTH, OCT had calcemic activity. These data demonstrate that OCT has calcemic activity, mainly in the bone, that is masked by its suppressive action on PTH. When compared to 1,25-(OH)2D3, however, the intrinsic calcemic activity of OCT is much less but its effects on PTH secretion are similar. Thus, OCT may be ideal for the treatment of the secondary hyperparathyroidism of chronic renal failure. |
| Document Type: Article |
| Language: English |
Addresses:
1. WASHINGTON UNIV, SCH MED, DEPT MED, CTR CHROMALLOY AMER KIDNEY, DIV RENAL, 4949 BARNES PLAZA, BOX 8129, ST LOUIS, MO 63110 USA
2. CHUGAI PHARMACEUT CO LTD, TOKYO 171, JAPAN |
| Publisher: BLACKWELL SCIENCE INC, 350 MAIN ST, MALDEN, MA 02148 |
| Subject Category: Endocrinology & Metabolism |
| IDS Number: JD680 |
| ISSN: 0884-0431 |
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