Mechanism of action of ghrelin

• Project/Area Number: 13671148
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• 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)
• Project Period (FY): 2001 – 2002
• Project Status: Completed(Fiscal Year 2002)
• Budget Amount: ¥4,100,000 (Direct Cost : ¥4,100,000); Fiscal Year 2002 : ¥1,600,000 (Direct Cost : ¥1,600,000); Fiscal Year 2001 : ¥2,500,000 (Direct Cost : ¥2,500,000)
• Keywords: Ghrelin / Grow hormone / Channel / alectrophysiology / secretion / Ghrelin / channel / electro physiology / secretion / ghrelin(グレリン) / 成長ホルモン / イオンチャネル / 電気生理学 / 非選択性腸イオン電流 / 細胞内カルシウム濃度 / ホルモン分泌

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.

Research Products

• [Publications] Sandrini F et al.: "PRKAR1A, one of the Carney Complex genes"J. Med. Genet. 39. e78-e88 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tamura Y et al.: "A Kindred of familial acromegaly without evidence for linkage to MEN-1 locus"Endocr. J. 49. 425-431 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] K Takano.K et al.: "Ionic mechanism of action of ghrelin"Proc. of Endocine. Soc. 524 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] K Takano K et al.: "Mechanism of action of ghrelin"Proc. 6th Pituitary Congress. 87 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takano, K., J. Yasufuku-Takano, A, Teramoto, and T. Fujita.: "Ionic mechanism of action of ghrelin on human GH-secreting cells"Proc. Endoc. Soc.. 524 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takano, K., J. Yasufuku-Tkano, A. Teramoto, and T. Fujita.: "Mechanism of action of ghrelin on human somatotroph adenoma cells"Proc. 6^<th> Pituitary Congress.. 87. (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [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
• [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
• [Publications] Sandrini, F et al.: "PKAR1A, one of the Carney complex genes"J.Med Genet.. 39(12). e75-e85 (2002)
• [Publications] Tamura, Y et al.: "A Kindred of familial acromegaly without evidence of ・・・"Endocrine J. 49(4). 425-431 (2002)
• [Publications] Takano, K et al.: "Iionic mechanism of action shrelin on human GH-secretins cells"Prac.Endocrine Society. 524 (2001)
• [Publications] Takano, K. et al.: "Mechanism of action of ghrelin on human somatotroph adenoma cells"Proc.6^<th> Pituitary Congress. 87 (2001)
• [Publications] Koji Takano et al.: "Ghrelin excites human GH secreting cells"Proceedings of the 83rd Endocine Society's Annual Meeting. 234 (2001)
• [Publications] Koji Takano et al.: "Ionic Mechanism of Ghrelin-Induced GH secretion"Proceedings of the 7^<th> International Pitaitary Congress. 60 (2001)
• [Publications] Toshio Ichikawa et al.: "Estrogenic Imparities in Plastic Labwares"Nature Biotechnology. 19. 812 (2001)