| Project/Area Number |
09470223
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
SEINO Yoshiki Okayama University Medical School, Professor, 医学部, 教授 (80028620)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Masaru Okayama University Medical School, Hospital, Lecturer, 医学部・附属病院, 講師 (20253023)
TANAKA Hiroyuki Okayama University Medical School, Hospital, Lecturer, 医学部・附属病院, 講師 (80231413)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,100,000 (Direct Cost: ¥12,100,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | secondary hyperparathyroidism / calcium sensing receptor / polymorphism / intracellular calcium / inositol tris phosphate / 副甲状腺機能亢進症 / 糖尿病性腎症 / 変異 / 2次性副甲状腺機能亢進症 / 慢性腎不全 / 副甲状腺ホルモン / 新生児重症副甲状腺機能亢進症 / 家族性低カルシウム尿性高カルシウム血症 / カルシウム感受性受容体 / 遺伝子変異 / 強制発現 / HEK293 / IP_3 |
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| Research Abstract |
The management of secondary hyperparathyroidism and renal osteodystrophy in end-stage renal failure is an important clinical problem. For the development of new and ideal methodologies, it is essential to know the pathophysiologic mechanisms of the parathyroid hormone secretion and the parathyroid cellular proliferation. To this aid, we have investigated the function of the calcium sensing receptor (Casr).
We have already identified several mutations in neonatal severe hyperparathyroidism. To clarify the function of these mutant Casr, the mutants produced by site directed mutagenesis were expressed in HEK 293 cell and the response to the change in extracellular calcium concentration was evaluated by measuring intracellular calcium concentration and inositol tris phosphate production. In these experiments, we confirmed that these mutants were functionless. This result in hands, we next explored the effects of Casr in the cellular proliferation and the effects of extracellular conditions on the function of the receptor. The results clearly indicated the close relationship between the function of receptor and the cellular proliferation, and suggested importance of the extracellular glucose concentration in its function. Moreover, we identified close relationship between the genetic polymorphism in the Casr gene and the severity of the secondary hyperparathyroidism.
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