1998 Fiscal Year Annual Research Report

循環関連ペプチドの中枢神経系における役割の解明

Research Project

Project/Area Number	10044332
Research Category	Grant-in-Aid for international Scientific Research
Section	Joint Research .
Research Institution	University of Occupational and Environmental Health, Japan
Principal Investigator	山下博産業医科大学, 医学部, 教授 (00030841)
Co-Investigator(Kenkyū-buntansha)	寒川賢治国立循環器病センター, 生化学部, 部長 (00112417) TRIBOLLET El ジュネーブ大学, 医学部, 講師 KOIZUMI Kiyo ニューヨーク州立大学, 医学部, 教授 KOW Lee Ming ロックフェラー大学, 神経生物&行動学, 助教授 VALE Wylie ソーク研究所, ペプチド生物学研究室, 教授
Keywords	循環 / ペプチド / 視床下部 / 室傍核 / 視索上核 / イオンチャネル / 学習
Research Abstract	循環関連ペプチドの中枢神経系における役割を遺伝・分子レベルから行動レベルに至る各レベルで比較検討及び包括的な解析を行なうための国際共同研究が進められている。1、分子生物学的手法を用いた検索:バゾプレッシンの脳内での過剰発現マウス(遺伝性多飲マウス)のバゾプレッシンmRNAの分布を検索したところ視床下部室傍核および視索上核、また正常マウスではほとんど発現していない部位である室傍核前部にも強い発現が見られた。2、新たな循環関連ペプチドの検索:GC-C受容体の内因性のリガンドとしてウログアニリンを同定し、そのアミノ酸構造、塩基配列および生体内分布を検索した。3、細胞内情報伝達系および電気生理学的検討:脳スライス標本を用いて検索により、PACAPおよびプロスタグランデインE2はラット視索上核の神経分泌細胞の神経活動を非選択性陽イオンチャネルを開くことにより興奮させた。単離したラット視索上核の神経分泌細胞の細胞内カルシウム濃度をPACAPは特異的な受容体を介して増加させた。4、循環関連ペプチドの自律神経系への関与:覚醒ラットの脳室内にアドレノメデュリンを投与すると室傍核および視索上核のオキシトシン産生ニューロンが特異的に活性化し、血中オキシトシン濃度が増加することを明らかにした。5、高次機能に及ぼす影響:遺伝性多飲マウスを用いて受動回避学習、シャトル回避学習およびモリス水迷路学習について検討したところ、学習・記憶能力が優れている傾向ことが示唆されたがさらに詳細な検討が必要である。

Research Products

(29 results)

All Other

All Publications (29 results)

[Publications] 上田陽一,他: "アドレノデュリンの中枢円分布" 医学のあゆみ. 184 (1). 31-33 (1998)
[Publications] Shibuya,I. et al.: "PACAP increases the cytosolic Ca^<2+> concentration and stimulates somatodendritic vasopressin release in rat supraoptic neurons." Journal of Neuroendocrinology. 10 (1). 31-42 (1998)
[Publications] Inenaga,K. et al.: "Glutamatergic synaptic inputs tomouse supraoptic neural in calcium-free medium in vitro." Journal of Neuroendocrinology. 10 (1). 1-7 (1998)
[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 Consezous Rat" Endocrinology. 138 (1). 383-388 (1998)
[Publications] Uezono,Y. et al: "Activationof inwardly rectifying K^+ channels by GABA-B receptors expressed in xenopus oocytes." Neuroreport. 9 (4). 583-587 (1998)
[Publications] Ueta,Y. et al.: "Hypovolemia upregulates the expression of neuronal nitric oxide synthase gene in the paraventricular and supraoptic nucle〓 of rats" Brain Research. 790. 25-32 (1998)
[Publications] 澁谷泉,他: "サイトカインにより内分泌反応" CLINICAL NEUROSCIENCE. 16 (4). 60-63 (1998)
[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
[Publications] Hattori,Y. et al.: "Ionotropic and metabotropic glutamate receptor agonist-indmed 〔Ca^<2+>〕 i increase in isolated rat supraoptic neuons." Journal of Neuroendocrinology. 10 (5). 383-389 (1998)
[Publications] Uezono,Y. et al.: "Adrenomedullin increases intracellular Ca^<2+> and inositol 14.5-trisphosphate in human oligodendroglial cell line KGIC." Brain Research. 786. 230-234 (1998)
[Publications] Harayama,N. et al.: "Ingibition of N-and P/Q-type calcium channels by postsynaptic GABAB receptor activation in rat sapraoptic neurobs." Joural of Physiology. 509 (2). 371-383 (1998)
[Publications] Serino,R. et al.: "Upregulation of hypothalamic nitric oxide synthase gene expression in streptozotocin-induced diabetic rats." Diabetologia. 41 (6). 640-648 (1998)
[Publications] Ueta,Y. et al.: "Neuronal nitric oxide synthase gene expression in human pituitary tumors: a possible association with somatotpoph adenomas and growth normonds-releastng hormore gene expression." Clinical Endocrinology. 49. 29-38 (1998)
[Publications] 上田陽一,他: "アドレノメデュリンと中枢神経系" Molecular Medicine特集アドレノメジュリンの基礎とその臨床応用. 35 (8). 998-1005 (1998)
[Publications] Tanaka,K. et al.: "Pituitary adenylate cydase-actirating polypeptide causes Ca^<2+> release from rganodinelcaffe the stores through a novel pathway independent of both inositol triphosphates and cyclic" Journa of Neurochemistry. 70. 1652-1661 (1998)
[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)
[Publications] Wang,U. -F. et al.: "Inhibition of spontaneous inhibitory postsynaptic currents (IPSC) by noradrenaline in rat supraoptic neurons through presynaptic α2-adrereceptor" Brain Research. 807. 61-69 (1998)
[Publications] Ibrahim,N. et al.: "GABA_B receptor-mediated ingibition of spontaneous action potential discharge in rat supraoptic neurons." Brain Research. 813. 88-96 (1998)
[Publications] Tanaka,K. et al: "Inhibition of voltage-dependent Ca^<2+> channels by prostagraninte in rat melanotrophs." Endocrinology. 139 (12). 4801-4810 (1998)
[Publications] Setiadji,V.S.: "Actions of prostaglandin E_<> on rat supraoptic neurons" Journal of Neuro endocrinology. 10 (12). 927-936 (1998)
[Publications] Shibuya,I. et al.: "Evidence that multiple P2X purinoceptors are functionally expressed in rat supraoptic neurons." Journal of Physiology. 514. 351-367 (1999)
[Publications] Date,Y. et al: "Orexins, orexinergic hypothalamic peptides, interact with automatic, neuroendocrire and neuroregulatory systems." Proc Natl.Acad.Sci.USA.96. 748-753 (1998)
[Publications] Ueta,Y. et al.: "Adrenomedullin-like immunoreactivity in the rat hypothalamo-neurohypophysial tract." Peptides. (in press).
[Publications] Yamamoto,Y. et al.: "Down regulation of the prepo-orexin gene expression in genetically obese mice." Molecular Brain Research. (in press).
[Publications] Nomura,M. et al.: "Effects of centrally odministered pituitary adenylate cyclase-activating polypeptideon c-fos gene expression and heteronuclear RNA for vasopressin in rat paraventricular and supraoptic nuclei." Neuroendocrinology. (in press).
[Publications] Serino, R. et al.: "Centrally odministered adrenomedullin increase plasma oyrocin level with induction of c-fos mRNA in the paraventricular and supraoptic nuclei of rat" Endocrinology. (in press).
[Publications] Date,Y. et al.: "Enterochromaffin-like cells, a cellular source of uroguanylin rat stomach." Endocrinology. (in press).
[Publications] Shibuya,I. et al.: "The Adrenal Chromaffin cell." Hokkaido Univ.Press.Sapporo, 13 (1998)
[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)

1998 Fiscal Year Annual Research Report

循環関連ペプチドの中枢神経系における役割の解明

Principal Investigator

山下 博 産業医科大学, 医学部, 教授 (00030841)

Research Products

[Publications] 上田 陽一,他: "アドレノデュリンの中枢円分布" 医学のあゆみ. 184 (1). 31-33 (1998)

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

[Publications] Inenaga,K. et al.: "Glutamatergic synaptic inputs tomouse supraoptic neural in calcium-free medium in vitro." Journal of Neuroendocrinology. 10 (1). 1-7 (1998)

[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 Consezous Rat" Endocrinology. 138 (1). 383-388 (1998)

[Publications] Uezono,Y. et al: "Activationof inwardly rectifying K^+ channels by GABA-B receptors expressed in xenopus oocytes." Neuroreport. 9 (4). 583-587 (1998)

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

[Publications] 澁谷 泉,他: "サイトカインにより内分泌反応" CLINICAL NEUROSCIENCE. 16 (4). 60-63 (1998)

[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

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

[Publications] Uezono,Y. et al.: "Adrenomedullin increases intracellular Ca^<2+> and inositol 14.5-trisphosphate in human oligodendroglial cell line KGIC." Brain Research. 786. 230-234 (1998)

[Publications] Harayama,N. et al.: "Ingibition of N-and P/Q-type calcium channels by postsynaptic GABAB receptor activation in rat sapraoptic neurobs." Joural of Physiology. 509 (2). 371-383 (1998)

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

[Publications] Ueta,Y. et al.: "Neuronal nitric oxide synthase gene expression in human pituitary tumors: a possible association with somatotpoph adenomas and growth normonds-releastng hormore gene expression." Clinical Endocrinology. 49. 29-38 (1998)

[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 アドレノメジュリンの基礎と その臨床応用. 35 (8). 998-1005 (1998)

[Publications] Tanaka,K. et al.: "Pituitary adenylate cydase-actirating polypeptide causes Ca^<2+> release from rganodinelcaffe the stores through a novel pathway independent of both inositol triphosphates and cyclic" Journa of Neurochemistry. 70. 1652-1661 (1998)

[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)

[Publications] Wang,U. -F. et al.: "Inhibition of spontaneous inhibitory postsynaptic currents (IPSC) by noradrenaline in rat supraoptic neurons through presynaptic α2-adrereceptor" Brain Research. 807. 61-69 (1998)

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

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

[Publications] Setiadji,V.S.: "Actions of prostaglandin E_<> on rat supraoptic neurons" Journal of Neuro endocrinology. 10 (12). 927-936 (1998)

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

[Publications] Date,Y. et al: "Orexins, orexinergic hypothalamic peptides, interact with automatic, neuroendocrire and neuroregulatory systems." Proc Natl.Acad.Sci.USA.96. 748-753 (1998)

[Publications] Ueta,Y. et al.: "Adrenomedullin-like immunoreactivity in the rat hypothalamo-neurohypophysial tract." Peptides. (in press).

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

[Publications] Nomura,M. et al.: "Effects of centrally odministered pituitary adenylate cyclase-activating polypeptideon c-fos gene expression and heteronuclear RNA for vasopressin in rat paraventricular and supraoptic nuclei." Neuroendocrinology. (in press).

[Publications] Serino, R. et al.: "Centrally odministered adrenomedullin increase plasma oyrocin level with induction of c-fos mRNA in the paraventricular and supraoptic nuclei of rat" Endocrinology. (in press).

[Publications] Date,Y. et al.: "Enterochromaffin-like cells, a cellular source of uroguanylin rat stomach." Endocrinology. (in press).

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

[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)

山下博産業医科大学, 医学部, 教授 (00030841)

[Publications] 上田陽一,他: "アドレノデュリンの中枢円分布" 医学のあゆみ. 184 (1). 31-33 (1998)

[Publications] 澁谷泉,他: "サイトカインにより内分泌反応" CLINICAL NEUROSCIENCE. 16 (4). 60-63 (1998)

[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

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

[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)