| Project/Area Number |
15590969
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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 | The University of Tokyo |
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Principal Investigator |
TAKANO Koji The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (20236243)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Ion channels / Endocrine cells / ghrelin / IGF-1 / Hormone secretion / Cell Growth / Pituitary cells / Growth Hormone / 非選択性陽イオンチャネル / 下垂体腺腫 / TRP-V2 / Rab27 / Carney Complex / Gsα / electrophysiology |
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| Research Abstract |
The pharmacological differences between the nonselective cation channels activated by GHRH and ghrelin in human GH-secreting cells were investigated. These channels depolarizes the membrane and stimulates action potentials thus increase calcium influx through the voltage-gated calcium channels. Both channels were blocked by ruthenium red and Gd, permiated calcium. Other pharmacological techniques failed to discriminate these two channels, suggesting that the same nonselective channel is activated by these two GH-secretagogues. IGF-1 activates a nonselective cation channel in human GH-secreting adenoma cells. The channel permeates calcium and is blocked by ruthenium red but not by Gd suggsting that it belongs to TRPV channel family. The activation is through PI_3 kinase-mediated mechanism. High temperature (50℃) activated similar channel but capsaicin did not, suggesting that TRPV_2 channel is functional in these cells. Morpholino antisense technique demonstrated that TRPV_2 is activated by IGF-1. Blocking the channel attenuated IGF-1-induced phosphorylation of p70S6 kinase indicating that this channel plays a pivotal role in IGF-1 action. ACTH activates a nonselective cation channel in adrenal glomerulosa cells. PKA is involved in the mechanisms of activation. The characteristics of the ACTH-activated nonselective cation channel is investigated.
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