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The localization and physiological role of adrenomedullin and related-peptides in the central nervous system

Research Project

Project/Area Number 10218210
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

UETA Yoichi (2000-2002)  University of Occupational and Environmental Health, Department of Physiology, Professor, 医学部, 教授 (10232745)

山下 博 (1998-1999)  産業医科大学, 医学部, 教授 (00030841)

Co-Investigator(Kenkyū-buntansha) NOGUCHI Jun  University of Occupational and Environmental Health, Department of Physiology, Research Associate, 医学部, 助手 (00330978)
YAMASHITA Hiroshi  Kyushu Nutrition Welfare University, Professor, 食物栄養学部, 教授 (00030841)
上田 陽一  産業医科大学, 医学部, 講師 (10232745)
澁谷 泉  産業医科大学, 医学部, 助教授 (50162649)
Project Period (FY) 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥47,200,000 (Direct Cost: ¥47,200,000)
Fiscal Year 2002: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2001: ¥8,400,000 (Direct Cost: ¥8,400,000)
Fiscal Year 2000: ¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 1999: ¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 1998: ¥11,200,000 (Direct Cost: ¥11,200,000)
Keywordsadrenomedullin / blood-brain barrier / endothelial cells / central nervous system / cerebrospinal fluid / tight junction / stress / アドレノメデュリン / グリア細胞 / mRNA / RT-PCR怯 / RAMP-1,-2,-3 / 視床下部 / オキシトシン / バゾプレッシン / Fos蛋白 / 血圧 / 室傍核 / 視索上核 / 自律神経 / 神経内分泌
Research Abstract

Adrenomedullin (AM) isolated from the human pheochromocytoma is one of the potent hypotensive peptides. The purpose of the present study is to examine the physiological role of AM in the central nervous system (CNS). We have demonstrated that rat cerebral endothelial cells produce and secrete large amount of AM in vitro blood-brain barrier (BBB) preparation. The results obtained this year are as follow.
(1) The concentrations of AM in plasma collected from the jugular vain, the carotid artery and suprarenal posterior vena cava were measured in rats anesthetized with sodium pentbarbi tal. The highest concentration of AM in plasma was collected samples from the jugular vein.
(2) Percutaneous cisternal cerebrospinal fluid (CSF) taps were performed in rats to determine the concentration of AM in the CSF. The concentration of AM in the CSF of rats anesthetized with ether showed higher than those with isoflurane. The concentration of AM in the CSF increased over 3-4 folds higher than the control at 5 and 7 days during drinking 2% saline.
(3) Chronic AM exposure increase transendothelial electrical resistance in vitro BBB, suggesting a tightening of intercellular junctions. There was no significant effect of AM on the expression of tight junction proteins (claudin-1, occludin and ZO-1). Chronic AM treatment in vitro BBB may influence the localization of these proteins without a change in protein expression.

Report

(6 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report

Research Products

(60 results)

All Other

All Publications (60 results)

  • [Publications] Kis, B.et al.: "Cerebral endothelial cells are a major source of adrenomedullin"Journal of Neuroendocrinology. 14. 283-293 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kis, B.et al.: "Adrenomedullin and migraine"Headache. 42. 1064-1065 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 芹野良太, 他: "アドレノメデュリンと血液脳関門"血管. 25. 165-169 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueta, Y. et al.: "The gene expression in the supraoptic nucleus"Microscopy Research and Technique. 56. 158-163 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita, H. et al.: "Electrophysiological and molecular properties of the oxytocin-and vasopressin-secreting systems in mammals"Hormones, Brain and Behavior. 4. 1-49 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kis, B.et al.: "Adrenomedullin, an autocrine mediator of blood-brain barrier function"Hypertension Research. 26. S61-S70 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kis, B. et al.: "Cerebral endothelial cells are a major source of adrenomedullin"Journal of Neuroendocrinology. 14. 283-293 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kis, B. et al.: "Adrenomedullin and migraine"Headache. 42. 064-1065 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueta, Y. et al.: "The gene expression in the supraoptic nucleus"Microscopy Research and Technique. 56. 158-163 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita, H. et al.: "Electrophysiological and molecular properties of the oxytocin- and vasopression-secreting systems in mammals"Hormones, Brain and Behavior. 4. 1-49 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kis, B. et al.: "Adrenomedullin, an autocrine mediator of blood-brain barrier function"Hypertension Research. 26. S61-S70 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kis, B., et al.: "Cerebral endothelial cells are a major source of adrenomedullin"Journal of Neuroendocrinology. 14. 283-293 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kis, B., et al.: "Adrenomedullin and migraine"Headache. 42. 1064-1065 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 芹野良太 他: "アドレノメデュリンと血液脳関門"血管. 25. 165-169 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ueta, Y., et al.: "The gene expression in the supraoptic nucleus"Microscopy Research and Technique. 56. 158-163 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita, H., et al.: "Electrophysiological and molecular properties of the oxytocin-and vasopressin-secreting systems in mammals"Hormones, Brain and Behavior. 4. 1-49 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kis, B., et al.: "Adrenomedullin, an Autocrine Mediator of Blood-Brain Barrrier Function"Hypertens Res. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kis B et al.: "Adrenomedullin regulates blood-brain barrier functions in vitro"Neuroreport. 12. 4139-4142 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Uezono Y et al.: "Production of cAMP by adrenomedullin in human oligodendroglial cell line KG1C : comparison with calcitonin gene-related peptide and amylin"Molecular Brain Research. 97. 59-69 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ueta Y et al.: "Action sites of adrenomedullin in the rat brain : Functional mapping by Fos expression"Peptides. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kis B et al.: "Cerebral endothelium is a major source of adrenomedullin"Journal of Neuroendocrinology. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kis B et al.: "Adrenomedullin in the cerebral circulation"Peptides. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Ueta Y. et al.: "A physiological role for adrenomedullin in rats; a potent hypotensive peptide in the hypathalamo-neurohypophysial system"Experimental Physiology. 85S. 163S-169S (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hara Y. et al.: "Increased urocortin-like immunoreactivity in the supraoptic nucleus of rats with aging"Biomedical Research. 21. 213-216 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kuru M. et al.: "Centrally administered orexin/hypocretin activates HPA axis in rats"Neuro Report. 11. 1977-1980 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamamoto Y. et al.: "Postnatal development of ovexin/hypocretin in rats"Molecular Brain Research. 78. 108-119 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nomura M. et al.: "Upregulation of synapsin IIa and IIb mRNAs in the paraventricular and supraoptic nuclei in chronic salt loaded and lactating rats"Neuroscience Research. 37. 201-210 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nomura M. et al.: "Induction of Pituitary adenylate cyclase-activating polypeptide mRNA in the medial parvicellular pant of the paraventricular nucleus of rats following kainic-acid-induced seizure"Neuroendocrinology. 71. 318-326 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueta Y. et al.: "Adrenomedullin-like immunoreactivity in the rat hypothalamo-neurohypophysical tract"Peptides. 20. 199-204 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Serino R. et al.: "Centrally administered adrenomedullin increases Plasma oxytocin level with induction of c-fos messenger ribonucleic acid in the paraventricular and supraoptic nuclei of tha rat."Endocrinology. 140. 2334-2342 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueta Y. et al.: "A physiological role for adrenomedullin in rats, a potent hypotensive peptide in the hypathalams-neurohypophysical system."Experimental Physiology. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] 上田 陽一・他: "アドレノメデュリンの中枢内分布" 医学のあゆみ. 184(1). 31-33 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shibuya,I.et al.: "PACAP increases the cytosolic Ca^<2+> concentration and stimulates somatodendritic vasopressin release in rat supraoptic ncurons." Journal of Neuroendocrinology. 10(1). 31-42 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Inenaga,K.et al.: "Glutamatergic synaptic inputs to mouse supraoptic neurons in calcium-free medium in vitro." Journal of Neuroendocrinology. 10(1). 1-7 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamamoto,S.et al.: "Centrally Administered Parathyroid Hormone(PTH)-Related Protein(1-34) But Not PTH(1-34) Stimulates Arginine-Vasopressin Secretion and It's Messenger RNA Expression in SON of the Conscious Rats." Endocrinology. 138(1). 383-388 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uezono,Y.et al: "Activation of inwardly rectifying K^+ channels by GABA-B receptors expressed in xenopus oocytes." Neuro report. 9(4). 583-587 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ueta,Y.et al.: "Hypovolemia upregulates the expression of neuronal nitric oxide synthase gene in the paraventricular and supraoptic nuclei of rats." Brain Research. 790. 25-32 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 澁谷 泉.他: "サイトカインによる内分泌反応" CLINICAL NEUROSCIENCE. 16(4). 60-63 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 上田 陽一他: "一酸化窒素(NO)と神経内分泌系" 脳機能の解明-21世紀に向けて-. 31. 351-354

    • Related Report
      1998 Annual Research Report
  • [Publications] Hattori,Y.et al.: "Ionotropic and metabotropic glutamate receptor agonist-induced 〔Ca^<2+>〕i increase in isolated rat supraoptic neurons." Journal of Neuroendocrinology. 10(5). 383-389 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Uezono,Y.et al.: "Adrenomedullin increases intracellular Ca^<2+> and inositol 1,4,5-trisphosphate in human oligodendroglial cell line KG-lC." Brain Research. 786. 230-234 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Harayama,N.et al.: "Inhibition of N-and P/Q-type calcium channels by postsynaptic GABA_B receptor activation in rat supraoptic neurons." Joural of Physiology. 509(2). 371-383 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Serino,R.et al.: "Upregulation of hypothalamic nitric oxide synthase gene expression in streptozotocin-induced diabetic rats." Diabetologia. 41(6). 640-648 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ueta,Y.et al.: "Neuronal nitric oxide synthase gene expression in human pituitary tumcts:a possible association with somatotroph adenomas and growth normontis-releasing hermene gene expression." Clinical Endocrinology. 49. 29-38 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 上田 陽一・他: "アドレノメデュリンと中枢神経系" Molecular Medicine 特集 アドレノメデュリンの基礎とその臨床応用. 35(8). 998-1005 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka,K.et al.: "Pituitary adenylate cydase-activating polypeptide causes Ca^<2+> release from rganodine/caffe ine stores through a novel pathway independent of both inositol triphosphates and cyclic" Journal of Neurochemistry. 70. 1652-1661 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shibuya,I.et al: "Patch-clamp analysis of the mechanism of PACAP-induced excitation in rat supraoptic neurons." Joural of Neuroendocrinology. 10(10). 759-768 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Wang,Y-F.et al.: "Inhibition of spontaneous inhibitory postsynaptic currents (IPSC) by noradrenaline in rat supraoptic neurons through presynaptic d2-adrenoceptors." Brain Reseavch. 807. 61-69 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ibrahim,N.et al.: "GABA_B receptor-mediated inhibition of spontaneous action potential discharge in rat supraoptic neurons." Brain Research. 813. 88-96 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka,K.et al: "Inhibition of voltage-dependent Ca^<2+> channels by prostagrandinE_2 in rat melanotrophs." Endocrinology. 139(12). 4801-4810 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Setiadji,V.S.: "Actions of prostaglandin E_2 on rat supraoptic neurons" Journal of Neuroendocrinology. 10(12). 927-936 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shibuya,I.et al.: "Evidence that multiple P2X purinoceptors are functionally expressed in rat supraoptic neurons." Journal of Physiology. 514. 351-367 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Date,Y.et al: "Orexins,orexinergic hypothalamic peptides,interact with automatic,neuroendocrine and neuroregulatory systems." prov Natl.Acad.sci.USA.96. 748-753 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ueta,Y.et al.: "Adrenomedullin-like immunoreacrivity in the rat hypothalamo-neurohypophysial tact." Peptides. in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamamoto,Y.et al.: "Down regulation of the prepo-orexin gene expression in genetically obese mice" Molecular Brain Research. in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Nomura,M.et al.: "Effects of centrally administered pituitary adenylate cyclase activating polypeptide on c-fos gene expression and heteronuclear RNA for vasopressin in rat paraventricular and supraoptic nuclei." Neuroendocrinology. in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Serino,R.et al.: "Centrally administered adrenomedullin increase plasma oytocin level with induction of c-fos mRNA in the paraventricular and supraoptic nuclei of rat" Endocrinology. in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Date,Y.et al.: "Enterochromaffin-like cells,a cellular source of uroguanylin rat stomach." Endocrinology. in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Shibuya,I.et al.: "The Adrenal Chromaffin cell." Hokkaido Univ.Press.Sapporo, 13 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 山下 博.他: "脳と循環-血圧は脳によって調節される" 共立出版,東京, (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2018-03-28  

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