| Co-Investigator(Kenkyū-buntansha) |
SHO Kimie Gunma University, Institute for Mol.and Cell.Regul., Asistant, 生体調節研究所, 教務員 (40201561)
TOMURA Hideaki Gunma University, Institute for Mol.and Cell. Regul., Assistant Professor, 生体調節研究所, 助手 (70217553)
KONDO Toshihiko Gunma University, Institute for Mol.and Cell. Regul., Associate Professor, 生体調節研究所, 講師 (10162108)
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| Research Abstract |
We have recently found that adenosine inhibits TSH-induced activation of adenylyl cyclase/cAMP system and enhances TSH-induced activation of phospholipase C/Ca^<2+> system in rat thyroid cells. In thyroid cells, in addition to norepinephrine, acetylcholine and ATP,lysosphingolipids such as sphingosine 1-phosphate (SlP) and sphingosylsphosphorylcholine (SPC) has also been suggested to be a potent Ca^<2+> mobilizer. In this study, we planned to clarify the roles of phospholipase C/Ca^<2+> system in thyroid cells. We obtained the following novel findings. (1) In human thyroid cells as well, it was demonstrated that phospholipase C/Ca^<2+> system was regulated through the cross-talk of TSH and adenosine. (2) To clarify the cross-talk mechanism by which TSH and adenosine regulate phospholipase C activity, we used in vivo Cos-7 cell reconstitution system, in which cDNAs encoding receptors, each wild type G-protein subunit and mutant subunit. We found that adenosine-induced modification of two TSH-induced responses were mediated by a single type of Gi protein, Gi2 or Gi3 ; alpha subunit mediates inhibition of AC and betagamma subunits activation of phospholipase C.(3) Grave's IgG in the presence of adenosine induced activation of phospholipase C/Ca^<2+> system, and hence it was suggested that the measurement of phospholipase C/Ca^<2+> system is applied for a novel diagnosis of Grave's disease. (4) SlP and SPC regulated phospholipase C/Ca^<2+> system, H_2O_2 generation, cell proliferation and so on in thyroid cells. Thus, these lipid mediators were suggested to be novel agonists in these cells.
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