2002 Fiscal Year Final Research Report Summary
Mechanism of action of ghrelin
Project/Area Number |
13671148
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Endocrinology
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Research Institution | The University of Tokyo |
Principal Investigator |
TAKANO Koji The University of Tokyo, Faculty of Medicine, research associate, 医学部附属病院, 助手 (20236243)
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Project Period (FY) |
2001 – 2002
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Keywords | Ghrelin / Grow hormone / Channel / alectrophysiology / secretion |
Research Abstract |
The mechanism of ghrelin-induced excitation of human GH-secreting cells was investigated using perforated- whole cell clamp technique and measurement of intracellular Ca^<2+> concentration [Ca^<2+>]I. Ghrelin depolarized GH-secreting human pituitary adenoma cells and increased action potential frequency. The depolarization was induced by a Na^+ influx through nonselective cation channels. The signal transduction of ghrelin-induced activation of the nonselective cation current involved protein kinase C. Ghrelin increased intracellular Ca^<2+> concentration of these cells depending mainly on the Ca^<2+> influx through the voltage-gated Ca^<2+> channels. This Ghrelin-induced increase in [Ca^<2+>]I was abolished in Na^+-free extracellular solution but was not abolished by tetrodotoxin, indicating that the ghrelin-induced cation current and depolarization are important in ghrelin-induced [Ca^<2+>]I increase. Ghrelin increased GH secretion dependency on the voltage-gated Ca^<2+> influx. In non-adenoma human GH-secreting cells, ghrelin-induced activation of a nonselective cation current and depolarization was also observed. These data indicate that ghrelin stimulates GH secretion by excitating these cells and increasing Ca^<2+> influx through the voltage-gated Ca^<2+> channels in human GH-secreting cells.
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Research Products
(8 results)
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[Publications] Sandrini F, Kirschner LS, Bei-T, Farmakidis C, Yasufuku-Takano J, Takano K: "Prezant TR, Marx SJ, Farrell WE, Clayton RN, Groussin L, Bertherat J, Stratakis CA. PRKAR1A, one of the Carney complex genes, and its locus (17q22-24) are rarely altered in pituitary tumours outside the Carney complex"J Med Genet.. 39(12). e78 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tamura Y, Ishibashi S, Gotoda T, Yasufuku-Takano J, Takano K, Ueki K, Yamashita S, Iizuka Y, Yahagi N, Shionoiri F, Okazaki H, Ohashi K, Osuga J, Harada K, Shimano H, Fujita T, Yamada N, Kimura S.: "A kindred of familial acromegaly without evidence for linkage to MEN-1 locus"Endocr J.. 49(4). 425-431 (2002)
Description
「研究成果報告書概要(欧文)」より