1998 Fiscal Year Annual Research Report

中枢におけるアドレノメデュリン及び関連ペプチドの局在とその作用

Research Project

Project/Area Number	10218210
Research Category	Grant-in-Aid for Scientific Research on Priority Areas (B)
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)	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)
Keywords	アドレノメデュリン / 神経内分泌 / 室傍核 / 視索上核 / オキシトシン
Research Abstract	アドレノメデュリンはヒト褐色細胞腫から発見された血管拡張性の新しい降圧ペプチドである。心・血管系のみならず中枢神経系にも存在しているが中枢におけるアドレノメデュリンの生理的意義の詳細は不明である。そこで我々は、アドレノメデュリンの脳内分布や投射部位および作用部位の検討を行ない、以下の結果を得た。 1. ラット視床下部室傍核および視索上核にアドレノメデュリン免疫陽性細胞が存在し、主にオキシトシンとの共存が認められた。軸策流を止めるためにコルヒチンをラット脳室内に投与したところ、室傍核および視索上核におけるアドレノメデュリン免疫陽性細胞の染色性が増強した。さらに、下垂体後葉への投射経路に結節状のアドレノメデュリン免疫陽性線維が観察され、アドレノメデュリンが視床下部から下垂体後葉に運ばれていることが推察された。下垂体切除ラットにおいても同様の結果が得られた。2.脳内アドレノメデュリンの作用部位を検討するために、アドレノメデュリンを脳室内に投与して、神経細胞活動の指標として汎用されているc-fos遺伝子の発現を調べた。その結果、視床下部室傍核および視索上核のオキシトシン産生ニューロンに特異的にc-fos遺伝子が発現することが明らかとなった。3.脳室内に投与したアドレノメデュリンが下垂体後葉からのオキシトシン分泌を惹起するかどうかを検討したところ、アドレノメデュリンを脳室内に投与すると血液中オキシトシン濃度が著明に増加することが明らかとなった。今後、中枢における内因性アドレノメデュリンの生理的役割、特に脳内オキシトシン系との関与についての検討を含め、多方面から検討していく必要がある。

Research Products

(29 results)

All Other

All Publications (29 results)

[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)
[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)
[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)
[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)
[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)
[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)
[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)
[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-induced 〔Ca^<2+>〕i increase in isolated rat supraoptic neurons." Journal of Neuroendocrinology. 10(5). 383-389 (1998)
[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)
[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)
[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 tumcts:a possible association with somatotroph adenomas and growth normontis-releasing hermene 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 特集アドレノメデ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-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)
[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,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)
[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)
[Publications] Tanaka,K.et al: "Inhibition of voltage-dependent Ca^<2+> channels by prostagrandinE_2 in rat melanotrophs." Endocrinology. 139(12). 4801-4810 (1998)
[Publications] Setiadji,V.S.: "Actions of prostaglandin E_2 on rat supraoptic neurons" Journal of Neuroendocrinology. 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,neuroendocrine and neuroregulatory systems." prov Natl.Acad.sci.USA.96. 748-753 (1998)
[Publications] Ueta,Y.et al.: "Adrenomedullin-like immunoreacrivity in the rat hypothalamo-neurohypophysial tact." 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 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.
[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.
[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

中枢におけるアドレノメデュリン及び関連ペプチドの局在とその作用

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: "アドレノメデュリンの中枢内分布" 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 ncurons." Journal of Neuroendocrinology. 10(1). 31-42 (1998)

[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)

[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)

[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)

[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)

[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)

[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-induced 〔Ca^<2+>〕i increase in isolated rat supraoptic neurons." Journal of Neuroendocrinology. 10(5). 383-389 (1998)

[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)

[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)

[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 tumcts:a possible association with somatotroph adenomas and growth normontis-releasing hermene 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 アドレノメデ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-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)

[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,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)

[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)

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

[Publications] Setiadji,V.S.: "Actions of prostaglandin E_2 on rat supraoptic neurons" Journal of Neuroendocrinology. 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,neuroendocrine and neuroregulatory systems." prov Natl.Acad.sci.USA.96. 748-753 (1998)

[Publications] Ueta,Y.et al.: "Adrenomedullin-like immunoreacrivity in the rat hypothalamo-neurohypophysial tact." 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 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.

[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.

[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: "アドレノメデュリンの中枢内分布" 医学のあゆみ. 184(1). 31-33 (1998)

[Publications] 澁谷泉.他: "サイトカインによる内分泌反応" 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 特集アドレノメデ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)