2007 Fiscal Year Final Research Report Summary
Stimulation of calcium-sensing receptor truncate human (1-84) parathyroid hormone amino-terminally
| Project/Area Number |
18591033
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Osaka City University |
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Principal Investigator |
IMANISHI Yasuo Osaka City University, Graduate School of Medicine, Lecturer (50326253)
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| Co-Investigator(Kenkyū-buntansha) |
INBA Masaaki OSAKA CITY UNIVERSITY, Graduate School of Medicine, Associate Professor (00176405)
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| Project Period (FY) |
2006 – 2007
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| Keywords | parathyroid hormone / extracellular calcium / peptide fragmentation / primary cultured parathyroid cells / cinacalcet |
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| Research Abstract |
Cinacalcet HC1 (cinacalcet), a calcimimetic compound which activates calcium-sensing receptor (CaR), has a magnificent effect of decreasing circulating PTH levels in both primary and secondary hyperparathyroidisms. Cinacalcet also suppressed the PTH secretion in vitro in primary cultured human parathyroid cells. Recently increasing extracellular Ca^<2+> concentration reported not only to suppress (1-84) PTH secretion but also to accelerate amino-terminal (N-terminal) truncation of (1-84) PTH in vitro. Our objective was to determine whether activation of CaR would enhance this truncation activity. N-terminally truncated fragments were detectable with commercially available intact PTH (I-PTH) assays, but not with the bio-intact PTH (Bio-PTH) assays, which detected only the (1-84) PTH. Suppression of PTH secretion by increasing the extracellular Ca^<2+> concentration (0.5-3.0 mM) or cinacalcet (10-1000 nM) was more evident with the Bio-PTH assay than with I-PTH assay for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism in vitro. The Bio-PTH/I-PTH ratio, which is the ratio of (1-84) PTH to the sum of (1-84) PTH and N-terminally truncated fragments, decreased in response to increase both in extracellular Ca^<2+> and cinacalcet concentrations. These findings suggest that the N-terminal truncation is enhanced by stimulation of CaR to suppress (1-84) PTH secretion and to generate N-terminally truncated PTH fragments.
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[Journal Article] Influence of nutritional status on serum large N-truncated PTH, but not PTH(1-84) in hemodialysis patients2007
Author(s)
Shidara, K, Inaba, M, Okuno, S, Imanishi, Y, Yamakawa, T, Ishimura, E, Kumeda, Y, Nishizawa, Y
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Journal Title
Biomed Pharmacother 61
Pages: 142-7
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism2007
Author(s)
Kawata, T, Imanishi, Y, Kobayashi, K, Miki, T, Arnold, A, Inaba, M, Nishizawa, Y
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Journal Title
J Am Soc Nephrol 18
Pages: 2683-8
Description
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[Journal Article] Glycated Albumin Is a Better Glycemic Indicator than Glycated Hemoglobin Values in Hemodialysis Patients with Diabetes Effect of Anemia and Erythropoietin Injection2007
Author(s)
Inaba, M, Okuno, S, Kumeda, Y, Yamada, S, Imanishi, Y, Tabata, T, Okamura, M, Okada, S, Yamakawa, T, Ishimura, E, Nishizawa, Y
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Journal Title
I Am Soc Nephrol 18
Pages: 896-903
Description
「研究成果報告書概要(欧文)」より
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