| 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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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | parathyroid hormone / extracellular calcium / peptide fragmentation / primary cultured parathyroid cells / cinacalcet / アミノ基末端断片化機構 / カルシウム感知受容体 / 原発性副甲状腺機能亢進症 |
|---|
| 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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