Studies on the signal transduction system of platelet collagen receptor that is related to species difference of hemostasis

• Project/Area Number: 15580261
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: University of Miyazaki
• Principal Investigator: ITO Katsuaki University of Miyazaki, Faculty of Agriculture, Professor, 農学部, 教授 (70136795)
• Co-Investigator(Kenkyū-buntansha): MOROI Masaaki Kurume University, Institute of Life Science, Professor, 分子生命科学研究所, 教授 (00049074)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥3,800,000 (Direct Cost: ¥3,800,000); Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000); Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
• Keywords: collagen / species difference / ADP / thromboxane A2 / platelet aggregation / synergism / signal transduction system / Chediak-Higashi syndrome / 凝集 / Chedaik-Higashi症候群 / 血小板

Research Abstract

Collagen-platelet interaction is important for hemostasis. Although collagen-induced platelet activation differs depending on species, little is known about the mechanism of platelet aggregation in animals other than humans. Collagen releases ADP from dense granules and generates thromboxane A2 (TXA_2) and these agonists in turn enhance the collagen action. In this study we investigated the roles of ADP and TXA_2 in the collagen-induced aggregation of platelets from humans, cattle and rats and the signal transduction system involved in the linkage of the collagen receptor and the roles of endogenous agonists.
Collagen-induced aggregation of human platelets highly depended on TXA_2 and that of rat platelets depended on ADP. The response of bovine platelets to a low dose of collagen required both of ADP and TXA_2 because either of actions of TXA_2 or ADP was blocked the action of the other endogenous agonist did not appear. Thus, TXA_2 plays an important role in the collagen-induced aggre gation of bovine platelets when cooperated with ADP. However, the production of TXA_2 due to collagen was less in bovine platelets than in human ones. Furthermore, it is suggested that the roles of phosphoinositide 3-kinase and protein kinase C in the collagen-induced release response and the direct action of collagen are different in bovine platelets from those in human platelets. Platelets from cattle with Chediak-Higashi syndrome(CHS) showed much less release of ADP and this might be due to very scarce ADP content in dense granules. It is suggested that the signal to stimulate ADP release and generate TXA_2 was not impaired in CHS platelets, although the signal related to Ca^<2+> mobilization by the direct action of collagen was greatly impaired. Thus, in the downstream of collagen receptor it seems that the signal transduction system to mobilize endogenous agonists and that related to the direct action of collagen are different and that the former system is not impaired in CHS platelets.

Research Products

• [Journal Article] Inhibition of protein kinase C-mediated contraction by Rho kinase inhibitor fasudil in rabbit aorta (2004)
  • Author(s): Shimomura, E., Shiraishi, M., Ikeda, M., Ito, K.et al.
  • Journal Title: Naunyn-Schmiedeberg's Arch.Pharmacol. 370(5) Pages: 414-422
  • NAID: 120007123678
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Inhibition of protein kinase C-mediated contraction by Rho kinase inhibitor fasudil in rabbit aorta. (2004)
  • Author(s): Shimomura, E., Shiraishi, M., Iwanaga, T., Seto, M., Sasaki, S., Ikeda, M., Ito, K.
  • Journal Title: Naunyn-Schmiedeberg's Arch.Pharmacol. 370(5) Pages: 414-422
  • NAID: 120007123678
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Essential role of Rho kinase in Ca^<2+> sensitization of prostaglandin F2・-induced contraction of rabbit aortae (2003)
  • Author(s): Ito, K., Shimomura, E., Iwanaga, T.et al.
  • Journal Title: J.Physiol.(Lond.) 546(3) Pages: 823-836
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A new monoclonal antibody, mAb 204-11, that influence the binding of platelet GPVI to fibrous collagen (2003)
  • Author(s): Moroi, M., Mizuguchi, J., Kawashima, S., Ito, K., Jung, S.M.et al.
  • Journal Title: Thrombosis Haemostasis 89(6) Pages: 996-1003
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Essential role of Rho kinase in Ca^<2+> sensitization of prostaglandin F2α-induced contraction of rabbit aortae. (2003)
  • Author(s): Ito, K., Shimomura, E., Iwanaga, T., Shiraishi, M., Shindo, K., Nakamura, J., Nagumo, H., Seto, M., Sasaki, Y., Takuwa, Y.
  • Journal Title: J.Physiol.(Lond.) 546(3) Pages: 823-836
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A new monoclonal antibody, mAb 204-11, that influences the binding of platelet GPVI to fibrous collagen (2003)
  • Author(s): Moroi, M., Mizuguchi, J., Kawashima, S., Nagamatsu, M., Miura, Y., Nakagaki, T., Ito, K, Jung, S.M.
  • Journal Title: Thrombosis Haemostasis 89(6) Pages: 996-1003
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A new monoclonal antibody, mAb 204-11, that influences the binding of platelet GPVI to fibrous collagen (2003)
  • Author(s): Moroi, M., Mizuguchi, J., Kawashima, S., Ito, K., Jung, S.M.et al.
  • Journal Title: Thrombosis Haemostasis 89(6) Pages: 996-1003
• [Publications] Moroi, M., Mizuguchi, J., Kawashima, S., Nagamatsu, M., Miura, Y., Nakagaki, T., Ito, K., Jung, S.M.: "A new monoclonal antibody, mAb 204-11, that influences the binding of platelet GPVI to fibrous collagen"Thrombosis Haemostasis. 89(6). 996-1003 (2003)