Purification and cloning of brain isoform of ADP-ribosyl cyclase

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 09480221
• 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, School of Medicine Professor, 医学部, 教授 (30093066)
• Co-Investigator(Kenkyū-buntansha): HOSHI Naoto Kanazawa University, School of Medicine Research Associate, 医学部, 助手 (90229170) ; TOKOYAMA Shigeru Kanazawa University, School of Medicine Associate Professor, 医学部, 助教授 (00210633) ; HASHII Minako Kanazawa University, School of Medicine Lecturer, 医学部, 講師 (10272957)
• Project Period (FY): 1997 – 1999
• Keywords: ADP-ribose / cyclic ADP ribose / cyclase / heart / ryanodine receptor / NAD

Research Abstract

We examined the role of cyclic ADP-ribose (cADP-ribose) as a second messenger downstream of adrenergic receptors in the heart after excitation of sympathetic neurons. To address this question, ADP-ribosyl cyclase activity was measured as the rate of [3H]cADP-ribose formation from [3H]NAD+ in a crude membrane fraction of rat ventricular myocytes. Isoproterenol at 1 mM increased ADP-ribosyl cyclase activity by 1.7-fold in venticular muscle ; This increase was inhibited by propranolol. The stimulatory effect on the cyclase was mimicked by 10 nM GTP and 10 mM GTP-g-S, while 10 mM GTP inhibited the cyclase. Cholera toxin blocked the activation of the cyclase by isoproterenol and GTP. The above effects of isoproterenol and GTP in ventricular membranes were confirmed by cyclic GDP-ribose formation fluorometrically. These results demonstrate the existence of a signal pathway from b-adrenergic receptors to membrane-bound ADP-ribosyl cyclase via G protein in the ventricular muscle cells, and suggest that increased cADP-ribose synthesis is involved in upregulation of cardiac function by sympathetic stimulation.

Research Products

• [Publications] Higashida, H. et al.: "Sympathetic potentiation of cyclic ADP-ribose formation in rat cardiac myocytes"J. Biol. Chem.. 274(47). 33348-33354 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Zhong, Z.-G. et al.: "Overexpression of rat synapsins in NG108-15 neuronal cells enhances function synapse formation with myotubes"Neurosci. Lett.. 260(1). 93-96 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takahashi, Y. et al.: "12-lipoxygenase overexpression in rodent NG108-15 cells enhances the excitability by inhibiting M-type K+ channels"J. Physiol. (London). 521(3). 567-574 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hashii, M. et al.: "cADP-ribose potentiates cytosolic Ca2+ elevation and Ca2+ entry via L-type voltage-activated Ca2+ channels in NG108-15 neuronal cells"Biochem. J.. 345(2). 207-215 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hotta, T. et al.: "Membrane-bound form of ADP-ribosyl cyclase in rat cortical astrocytes in culture"J. Neurochem.. 74(2). 669-675 (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Higashida, H. et al.: "Slow Synaptic Responses Modulation"Slow synaptic responses in neuronal tumor cells : dual regulation of ADP-ribosyl cyclase and inhibition of M-current by muscarinic receptor stimulation. 35-41 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Zhong, Zhen-Guo, Yokoyama, Shigeru, Noda, Mami and Higashida, Haruhiro: "Overexpression of adhesion molecule L1 in NG108-15 neuroblastoma x glioma hybrid cells enhances dibutyryl cAMP induced neurite outgrowth and functional synapse formation with myotubes."J. Neurochem.. 68. 2291-2299 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takanaga, Hitomi, Maeda, Hiroshi, Yabuchi, Hikaru, Tamai, Ikumi, Higashida, Haruhiro and Tsuji, Akira: "Nicotinic acid transport mediated by pH-dependent anion antiporter and protein cotransporter in rabbit intestinal brush-border membrane."J. Pharm. Pharmacol.. 48. 1073-1077 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tamai, Ikumi, Hayashi, Kiyomi, Terao, Toshimitsu, Sai, Yoshimichi, Shiraga, Toshiyuki, Miyamoto, Ken-ichi, Takeda, Eiji, Higashida, Haruhiro and Tsuji, Akira: "The predominant contribution of oligopeptide transporter PepT1 to intestinal absorption of b-lactam antibiotics in the rat small intestine."J. Pharm. Pharmacol.. 49. 796-801 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Taketo, Megumi, Yokoyama, Shigeru, Fukuda, Mitsunori, Mikoshiba, Katsuhiko and Higashida, Haruhiro: "Inositol-1,3,4,5-tetrakisphosphate binding sites in control and ras-transformed NIH/3T3 fibroblasts."Biochem. Biophys. Res. Commun.. 239. 349-352 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Higashida, Haruhiro, Yokoyama, Shigeru, Hashii, Minako, Taketo, Megumi, Higashida, Masaharu, Takayasu, Tatsunori, Ohshima, Tohru, Takasawa, Shin, Okamoto, Hiroshi and Noda, Mami: "Muscarinic receptor-mediated dual regulation of ADP-ribosyl cyclase in NG108-15 neuronal cell membranes."J. Biol. Chem.. 272. 31272-31277 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Higashida, Haruhiro: "ADP-ribosyl cyclase coupled with receptors via G proteins."FEBS Lett.. 418. 355-356 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ishizaka, Nobuto, Noda, Mami, Yokoyama, Shigeru, Kawasaki, Kazuo, Yamamoto, Miyuki and Higashida, Haruhiro: "Muscarinic acetylcholine receptor subtypes in the human iris."Brain Res.. 787. 344-347 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Higashida, Haruhiro, Hoshi, Naoto, Knijnik, Rimma, Zadina, James E., and Kastin, Abba J.: "Endomorphins inhibit high-threshold CaィイD12+ィエD1 channel currents in rodent NG108-15 cells overexpressing m-opioid receptors."J. Physiol. (Lond). 507. 71-75 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Furukawa, Taiji, Miura, Reiko, Mori, Yasuo, Strobeck, Mark, Suzuki, Kazuyuki, Ogihara, Yoshiyasu, Asano, Tomiko, Morishita, Rika, Hashii, Minako, Higashida, Haruhiro, Yoshii, Mitsunori and Nukada, Toshihide: "Differential interactions of the C terminus and the cytoplasmic I-II loop of neuronal CaィイD12+ィエD1 channels with G-protein a and bg subunits."J. Biol. Chem.. 273. 17595-17603 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hoshi, Naoto, Takahashi, Hiroto, Shahidullah, Mohammad, Yokoyama, Shigeru and Higashida, Haruhiro: "KCR1, a membrane protein that facilitates functional expression of non-inactivating KィイD1+ィエD1 currents associates with rat EAG voltage-dependent KィイD1+ィエD1 channels."J. Biol. Chem.. 273. 23080-23085 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Zhong, Zhen-Guo, Noda, Mami, Takahashi, Hiroto, Higashida, Haruhiro: "Overexpression of rat synapsins in NG108-15 neuronal cells enhances functional synapse formation with myotubes."Neurosci. Lett.. 260. 93-96 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takeda, Hisashi, Kimura, Yasuhito, Higashida, Haruhiro, and Yokoyama, Shigeru: "Localization of B2 bradykinin receptor mRNA in the rat retina and sclerocornea."Immunopharmacol.. 45. 51-55 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Higashida, Haruhiro, Taketo, Megumi, Takahashi, Hiroto, Yokoyama, Shigeru, and Hashii Minako: "Potential mechanism for bradykinin-activated and inositol tetrakisphosphate-dependent CaィイD12+ィエD1 influx by Ras and GAP1 in fibroblast cells."Immunopharmacol.. 45. 7-11 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Higashida, Haruhiro, Egorova, Alla, Higashida, Chiharu, Zhong, Zhen-Guo, Yokoyama, Shigeru, Noda, Mami and Zhang, Jia-Sheng: "Sympathetic potentiation of cyclic ADP-ribose formation in rat cardiac myocytes."J. Biol. Chem.. 274. 33348-33354 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takahashi, Yoshitaka, Kawajiri, Hiroo, Yoshimura, Tanihiro, Hoshi, Naoto and Higashida, Haruhiro: "12-lipoxygenase overexprssion in rodent NG108-15 cells enhances the excitability by inhibiting M-type KィイD1+ィエD1 channels."J. Physiol. (London). 521. 567-574 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hottra, Taeko, Asai, Kiyofumi, Fujita, Kaori, Kato, Taiji and Higashida, Haruhito: "Membrane-bound form of ADP-ribosyl cyclase in rat cortical astrocytes in culture."J. Neurochem.. 74. 669-675 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hashii, Minako, Minabe, Yoshio and Higashida, Haruhiro: "cADP-ribose potentiates cytosolic CaィイD12+ィエD1 elevation and CaィイD12+ィエD1 entry via L-type voltage-activated CaィイD12+ィエD1 channels in NG108-15 neuronal cells."Biochem. J.. 345. 207-215 (2000)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Higashida, Haruhiro, Zhang, Jia-Sheng and Takeda Yoshiyu: "Angiotensin II cyclac ADP-ribose formation in rat cardiac myocytes."Biochem. J.. (Submitted).
  • Description: 「研究成果報告書概要(欧文)」より