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A study on a role of endogenous neuropeptides in the brain in the regulation of hepatobiliary and pancreatic functions

Research Project

Project/Area Number 12670512
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionDokkyo University School of Medicine

Principal Investigator

YONEDA Masashi  Dokkyo University School of Medicine, Assistant Professor, 医学部, 講師 (30261407)

Co-Investigator(Kenkyū-buntansha) 寺野 彰  獨協医科大学, 医学部, 教授 (50155470)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordshepatic pathophysiology / neuropeptide / neurotransmitter / liver injury / stress / automatic nervous system
Research Abstract

A role of endogenous neuropeptides in the brain in the regulation of hepatic function was investigated in rats. Rats were anesthetized with urethane and positioned on stereotaxic apparatus. A probe of Laser Doppler flowmeter was placed on the surface of the liver. After 60 min stabilization, basal hepatic blood flow was measured for 30 min, and kainic acid was microinjected into the medullary raphe pallidus. Hepatic blood flow was observed for 120 min post peptide injection. Microinjection of kainic acid into the hemodynamics was reversed by pre-injection of polyclonal anti-TRH antibody in the cisterna magna. Rats were injected with CCl_4 (2ml/kg) subcutaneously and subjected to partial body restraint stress for 6h. CRF antagonist, astressin, was injected intracisternally just before and 6h after CCl_4 administration. Restraint stress exacerbated CCl_4-induced elevation of serum ALT from 293 +__- 11 IU/l to 398 +__- 35 IU/l. Intracisternal astressin dose-dependently inhibited the serum ALT elevation induced by restraint stress. Intracisternal astressin reduced CCl_4-induced liver histological change exacerbated by restraint stress. The exacerbating effect of restraint stress on CCl_4-induced liver damage was abolished by sympathectomy or 6-OHDA pretreatment but not by hepatic branch vagotomy or atropine pretreatment.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Nakade Y, Yoneda M, Nakamura K, Makino I, Terano A: "Involvement of endogenous CRF in carbon tetrachloride-induced acute liver injury in rats"Am J Physiol. 282(6). R1782-R1788 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura K, Ito T, Yoneda M, Takamoto S, et al.: "Antithrombin III prevents concanavalin A-induced liver injury through inhibition of macrophage inflammatory protein-2 release and production of prostacyclin in mice"J Hepatol. 36(6). 766-773 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kurosawa M, Unno T, Aikawa Y, Yoneda M: "Neural regulation of hepatic blood flow in rats : an in vivo study"Neurosci Lett. 321(3). 145-148 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoneda M, Kurosawa M, Watanobe H, Terano A: "Lafutidine increases hepatic blood flow via potentiating the action of central thyrotropin-releasing hormone in urethane-anesthetized rats"J Gastrol Hepatol. 18(2). 177-184 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanobe H, Yoneda M: "A mechanism underlying the sexually dimorphic ACTH response to lipopolysaccharide in rats : sex steroid modulation of cytokine binding sites in the hypothalamus"J Physiol. 547. 221-232 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakade Y, Yoneda M, Yokohama S, et al.: "Central injection of astressin inhibits carbon tetrachloride-induced acute liver injury in rats"Eur J Pharmacol. 460(2-3). 138-138 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 米田政志, 寺野 彰: "Annual Review 消化器 2003"中外医学社. 358 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kono T, Yoneda M, et al.: "Adaptive cytoprotection against acetic acid induced colonic injury in rates"Int Colorect Dis. 16. 384-390 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura K, Okada M, Yoneda M, et al.: "Macrophage inflammatory protein-2 induced by TNF-alpha plays a pivotal role in concanavalin A-induced liver injury in mice"J Hepatol. 35. 217-224 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanobe H and Yoneda M: "A significant participation of leukemia inhibitory factor in regulating the reproductive function in rats: a novel action of the pleiotropic cytokine"Biochem Biopyis Res Commun. 282. 643-646 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanobe H, Yoneda M, et al.: "Normalization of circulating leptin levels by fasting improves the reproductive function in obese OLETF female rats"Neuropeptides. 35. 45-49 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanobe H, Yoneda M, et al.: "Further evidence for a significant participation of the melanocortin 4 receptor in the preovulatory prolactin surge in the rat"Brains Res Bull. 54. 521-525 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yokohama S, Yoneda M, et al.: "Effect of central urcortin on carbon tetrachloride-induced acute liver injury in rats"Neurosci Lett. 313. 149-152 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasegawa T, Yoneda M, et al.: "Plasma transforming growth factor-beta 1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study"Aliment Pharmacol Ther. 15. 1667-1672 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyamoto Y, Yoneda M, et al.: "Gastric neuropeptides and gastric motor abnormality in streptozotocin-induced diabetic rats: observation for four weeks after streptozotocin"Dig Dis Sci. 46. 1596-1603 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakade Y, Yoneda M, et al.: "Involvement of endogenous CRF in carbon tetrachloride-induced acute liver injury in rats"Am J Physiol. 282(6). R1782-R1788 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakade Y, Yoneda M, et al: "Central injection of astressin inhibits carbon tetrachloride-induced acute liver injury in rats"Eur J Pharmacol. 460(2-3). 135-138 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanobe H, Yoneda M: "A mechanism underlying the sexually dimorphic ACTH response to lipopolysaccharide in rats: sex steroid modulation of cytokine binding sites in the hypothalamus"J Physiol. 547. 221-223 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoneda M, Kurosawa M, et al.: "Lafutidine increases hepatic blood flow via potentiating the action of central thyrotopin-releasing hormone in urethane-anethetized rats"J Gastrol Hepatol. 18(2). 177-184 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoneda M, Watanobe H and Terano A: "Regulation of hepatic function by brain neuropeptides"Current Topics in Peptide & Protein Research. 5. 97-100 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoneda M, Watanobe H and Terano A: "Central regulation of hepatic function by neuropeptides"J Gastroenterol. 36. 361-367 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoneda M, Kurosawa M, Watanobe H, Shimada T, Terano A: "Brain-gut axis of the liver: a role of central neuropeptides"J Gastroenterol. 37(Suppl). 361-367 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakade Y, Yoneda M, Nakamura K, Makino I, Terano A: "Involvement of endogenous CRF in carbon tetrachloride-induced acute liver injury in rats"Am J Physiol. 282(6). R1782-R1788 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura K, Ito T, Yoneda M, Takamoto S, et al.: "Antithrombin III prevents concanavalin A-induced liver injury through inhibition of macrophage inflammatory protein-2 release and production of prostacyclin in mice"J Hepatol. 36(6). 766-773 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kurosawa M, Unno T, Aikawa Y, Yoneda M: "Neural regulation of hepatic blood flow in rats : an in vivo study"Neurosci Lett. 321(3). 145-148 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoneda M, Kurosawa M, Watanobe H, Terano A: "Lafutidine increases hepatic blood flow via potentiating the action of central thyrotropin-releasing hormone in urethane-anesthetized rats"J Gastrol Hepatol. 18(2). 177-184 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watanobe H, Yoneda M: "A mechanism underlying the sexually dimorphic ACTH response to lipopolysaccharide in rats : sex steroid modulation of cytokine binding sites in the hypothalamus"J Physiol. 547. 221-232 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakade Y, Yoneda M, Yokohama S, et al.: "Central injection of astressin inhibits carbon tetrachloride-induced acute liver injury in rats"Eur J Pharmacol. 460(2-3). 138 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 米田政志, 寺野 彰: "Annual Review 消化器 2003"中外医学社. 358 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyamoto Y, Yoneda M, Morikawa A, Itoh H, Makino I: "Gastric neuropeptides and gastric motor abnormality in streptozotocin-induced diabetic rats : observation for four weeks after streptozotocin."Dig Dis Sci. 46. 1596-1603 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hasegawa T, Yoneda M, Nakamura K, Makino I, Terano A: "Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis : a pilot study."Aliment Pharmacol Ther. 15. 1667-1672 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yokohama S, Yoneda M, et al.: "Effect of central urocortin on carbon tetrachloride-induced acute liver injury in rats."Neurosci Lett. 313. 49-52 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Watanobe H, Yoneda M, Kakizaki Y, Kohsaka A, Suda T, Schioth HB: "Further evidence for a significant participation of the melanocortin 4 receptor in the preovulatory prolactin surge in the rat."Brain Res Bull. 54. 521-525 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Watanobe H, Yoneda M, Kohsaka A, Kakizaki Y, Suda T, Schioth HB: "Normalization of circulating leptin levels by fasting improves the reproductive function in obese OLETF female rats."Neuropeptides. 35. 45-49 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Watanobe H, Yoneda M: "A significant participation of leukemia inhibitory factor in regulating the reproductive function in rats : a novel action of the pleiotropic cytokine."Biochem Biophys Res Commun. 282. 643-646 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 米田政志, 島田忠人, 寺野彰: "ヘリコバクターピロリ胃炎"金原出版. 125 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hizume T,Watanobe H,Yoneda M,Suda T,Schioth H: "Involvement of Prolactin-releasing peptide in the preovulatory luteinizing hormone and prolactin surges in the rat"Biochem Biophys Res Commun. 279(1). 35-39 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kamiya K,Kono T,Iwamoto J,Yoneda M,Kotani H,Kasai S: "The cytoprotective role of lipopolysaccharide-induced nitric oxide against liver damage during early phase of endotoxemia in rats"Shock. 14(2). 229-233 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kono T,Nishida M,Inagaki N,Tanaka Y,Yoneda M and Kasai: "Development and Characterization of 1C6-203, a New Monoclonal Antibody Specific to Human Thymidine Phosphorylase"J Histochem Cytochem. 49(1). 131-137 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Watanobe H,Yoneda M,Kakizaki Y,Kohsaka A,: "Further evidence for a significant participation of the melanocortin 4 receptor in the preovulatory prolactin surge in the rat"Brain Res Bull. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoneda M and Terano A: "Central regulation of hepatic function by neuropeptides"Journal of Gastroenterology. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Watanobe H,Yoneda M: "A signufucant participation of leukemia inhibitory factor in regulating the reproductive function in rats : a novel action of the pleitropic cytokine"Biochem Biophys Res Comm. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] 米田政志,黒澤美枝子,寺野彰: "Annual Review消化器2000"中外医学社. 378 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 米田政志,寺野彰: "Annual Review消化器2001"中外医学社. 340 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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