ADP-ribosyl cyclase coupled with dopamine receptors : Application to Parkinson's disease

• Project/Area Number: 15300124
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kanazawa University
• Principal Investigator: HIGASHIDA Haruhiro Kanazawa University, Dept.of Biophysical Genetics, Professor, 医学系研究科, 教授 (30093066)
• Co-Investigator(Kenkyū-buntansha): YOKOYAMA S. Kanazawa University, Dept.of Biophysical Genetics, Associate Professor, 医学系研究科, 助教授 (00210633)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥14,200,000 (Direct Cost: ¥14,200,000); Fiscal Year 2005: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2004: ¥4,700,000 (Direct Cost: ¥4,700,000); Fiscal Year 2003: ¥5,800,000 (Direct Cost: ¥5,800,000)
• Keywords: Cyclic ADP-ribose / CD38 / NAD^+ / NG108-15 cells / Striatum / Dopamine / Dopamine receptor

Research Abstract

We examined the role of cyclic ADP-ribose (cADPR) as a second messenger downstream of receptors in the striatal cortex and NG108-15 cells. To address this question, ADP-ribosyl cyclase activity was measured in a crude membrane fraction of rat striatum and NG108-15 cells transfected with CD38. Dopamine (DA) stimulated the cyclase activity. The cyclase activity in overexpressed cells had various effects on neuronal function. The following two reports are the summary of the cADPR function written in a review form (7-2) and research report on CD38 transfection (7-3)

Research Products

• [Journal Article] Acetylcholine stimulates cyclic ADP-ribose formation via Ml muscarinic receptors in rat superior cervical ganglion. (2005)
  • Author(s): Zhang JS, Jin D, Higashida H.
  • Journal Title: Biochem Biophys Res Commun. 335 Pages: 920-924
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Amplification of depolarization-induced and ryanodine-sensitive cytosolic Ca2+ elevation by synthetic carbocyclic analogs of cyclic ADP-ribose and their antagonistic effects in NG108-15 neuronal cells. (2005)
  • Author(s): Hashii M, Shuto S, Fukuoka M, Kudoh T, Matsuda A, Higashida H.
  • Journal Title: Neurochem. 94 Pages: 316-323
  • NAID: 120000809381
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Synthesis of stable and cell-type selective analogues of cyclic ADP-ribose, a Ca(2+)-mobilizing second messenger. Structure--activity relationship of the N1-ribose moiety. (2005)
  • Author(s): Kudoh T, Fukuoka M, Ichikawa S, Murayama T, Ogawa Y, Hashii M, Higashida H, Kunerth S, Weber K, Guse AH, Potter BV, Matsuda A, Shuto S.
  • Journal Title: Am Chem Soc. 127 Pages: 8846-8855
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Induction of interleukin-6 in dorsal root ganglion neurons after gradual elongation of rat sciatic nerve. (2005)
  • Author(s): Osamura N, Ikeda K, Ito T, Higashida H, Tomita K, Yokoyama S.
  • Journal Title: Exp Neurol. 195 Pages: 61-70
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cyclin-dependent kinase 5 activators p35 and p39 facilitate formation of functional synapses. (2005)
  • Author(s): Johansson JU, Lilja L, Chen XL, Higashida H, Meister B, Noda M, Zhong ZG, Yokoyama S, Berggren PO, Bark C.
  • Journal Title: Brain Res Mol Brain Res. 138 Pages: 215-227
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Protein kinase C bound with A-kinase anchoring protein is involved in muscarinic receptor-activated modulation of M-type KCNQ potassium channels. (2005)
  • Author(s): Higashida H, Hoshi N, Zhang JS, Yokoyama S, Hashii M, Jin D, Noda M, Robbins J.
  • Journal Title: Neurosci Res. 51 Pages: 231-234
  • NAID: 10015451122
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Acetylcholine stimulates cyclic ADP-ribose formation via M1 muscarinic receptors in rat superior cervical ganglion. (2005)
  • Author(s): Zhang JS, Jin D, Higashida H.
  • Journal Title: Biochem Biophys Res Commun 335 Pages: 920-924
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Amplification of depolarization-induced and ryanodine-sensitive cytosolic Ca2+ elevation by synthetic carbocyclic analogs of cyclic ADP-ribose and their antagonistic effects in NG108-15 neuronal cells. (2005)
  • Author(s): Hashii M, Shuto S, Fukuoka M, Kudoh T, Matsuda A, Higashida H.
  • Journal Title: J Neurochem. 94 Pages: 316-323
  • NAID: 120000809381
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Synthesis of stable and cell-type selective analogues of cyclic ADP-ribose, a Ca(2+)-mobilizing second messenger. Structure-activity relationship of the N1-ribose moiety. (2005)
  • Author(s): Kudoh T, Fukuoka M, Ichikawa S, Murayama T, Ogawa Y, Hashii M, Higashida H, Kunerth S, Weber K, Guse AH, Potter BV, Matsuda A, Shuto S.
  • Journal Title: J Am Chem Soc. 127 Pages: 8846-8855
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Acetylcholine stimulates cyclic ADP-ribose formation via M1 muscarinic receptors in rat superior cervical ganglion. (2005)
  • Author(s): Zhang JS, Jin D, Higashida H.
  • Journal Title: Biochem Biophys Res Commun. 335 Pages: 920-924
• [Journal Article] Synthesis of stable and cell-type selective analogues of cyclic ADP-ribose, a Ca(2+)-mobilizing second messenger. Structure--activity relationship of the N1-ribose moiety. (2005)
  • Author(s): Kudoh T, Fukuoka M, Ichikawa S, Murayama T, Ogawa Y, Hashii M, Higashida H, Kunerth S, Weber K, Guse AH, Potter BV, Matsuda A, Shuto S.
  • Journal Title: J Am Chem Soc. 127 Pages: 8846-8855
• [Journal Article] Protein kinase C bound with A-kinase anchoring protein is involved in muscarinic receptor-activated modulation of M-type KCNQ potassium channels. (2005)
  • Author(s): Higashida H, Hoshi N, Zhang JS, Yokoyam S, Hashii M, Jin D, Noda M, Robbins J.
  • Journal Title: Neurosci Res. 51 Pages: 231-234
  • NAID: 10015451122
• [Journal Article] Multiple signal transduction pathways mediated by 5-HT receptors. (2004)
  • Author(s): Noda M, Higashida H, Aoki S, Wada K.
  • Journal Title: Mol Neurobiol 29 Pages: 31-39
• [Journal Article] Probucol aggravates long QT syndrome associated with a novel missense mutation M124T in the N-terminus of HERG. (2004)
  • Author(s): Hayashi K, Shimizu M, Ino H, Yamaguchi M, Terai H, Hoshi N, Higashida H, Terasima N, Uno Y, Kanaya H, Mabuchi H.
  • Journal Title: Clinical Science 107 Pages: 175-182
• [Journal Article] Draper-mediated and phosphatidylserine-independent phagocytosis of apoptotic cells by Drosophila hemocytes/macrophages. (2004)
  • Author(s): Manaka J, Kuraishi T, Shiratsuchi A, Nakai Y, Higashida H, Henson P, Nakanishi Y
  • Journal Title: J Biol Chem. 279 Pages: 48466-48476
• [Journal Article] Genes required for Drosophila nervous system development identified by RNA interference. (2004)
  • Author(s): Ivanov AI, Rovescalli AC, Pozzi P, Yoo S, Mozer B, Li HP, Yu SH, Higashida H, Guo V, Spencer M, Nirenberg M.
  • Journal Title: Proc Natl Acad Sci U S A. 101 Pages: 16216-16221
• [Patent(Industrial Property Rights)] パーキンソン病の治療のための医薬 (2005)
  • Inventor(s): 東田 陽博
  • Industrial Property Rights Holder: 金沢大学TLO
  • Industrial Property Number: 2005-189518
  • Filing Date: 2005-07-15
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yamaguchi, M., Shimizu, M., Ino, H., Terai, K., Hoshi, N., Higashida, H.: "Clinical and electrophysiological characterization of a novel mutation (F193L) in the KCNQ1 gene associated with long QT syndrome"Clinical Science. 104. 377-382 (2003)
• [Publications] Hoshi, N., Zhang, JS, Omaki, M., Yokoyama, S., Scott, JD, Brown, DA, Higashida, H.: "AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists"Nature Neurosci.. 6. 564-571 (2003)
• [Publications] Higashida, H., Zhang, JS, Mochida, S., Noda, M., Hoshi, N., Hashii, M., Yokoyama, S.et al.: "Subtype-specific coupling with ADP-ribosyl cyclase of metabotropic glutamate receptors in retina, cervical superior ganglion and NG108-15 cells"J.Neurochem.. 85. 1148-1158 (2003)
• [Publications] Noda, M., Higashida, H., Aoki, S., Wada K.: "Multiple signal transduction pathways mediated by 5-HT receptors"Mol.Neurobiol.. 29. 31-39 (2004)