1993 Fiscal Year Annual Research Report

薬物受容体の機能とその調節

Research Project

Project/Area Number	05304026
Research Institution	Shiga University of Medical Science
Principal Investigator	戸田昇滋賀医科大学, 医学部, 教授 (50025590)
Co-Investigator(Kenkyū-buntansha)	高柳一成東邦大学, 薬学部, 教授 (70012599) 安孫子保旭川医科大学, 医学部, 教授 (90041821) 斉藤秀哉北海道大学, 医学部, 教授 (20000929) 加藤隆一慶応義塾大学, 医学部, 教授 (40112685) 栗山欣弥京都府立医科大学, 医学部, 教授 (20079734)
Keywords	薬物受容体 / GABA受容体 / 一酸化窒素(NO) / エンドセリン / タキキニン受容体 / エタノール / セロトニン / ニコチン
Research Abstract	中枢神経系、心血管系および平滑筋の薬物受容体と細胞内情報伝達機構、神経伝達物質の作用などについて以下の成果が得られた。 1.中枢神経系:脳内GABA受容体の構造と機能に関する分子薬理学的研究の結果、GABA_B受容体のモノクロナル抗体を得た(栗山)。初代培養ニューロンを用いて、エタノールのGABA_A受容体での作用部位はベンゾジアゼパムのそれと異なるサブユニット又はチャンネルであるとの結論を得た(笹)。無麻酔ラットの脳を潅流し、セロトニンが5HT_3受容体を介して、カリウム刺激により生じたノルアドレナリン遊離を抑制する可能性を示した(斉藤)。タキキニンNK-3受容体の選択的作用薬センクタイドは視床下部のNK-3受容体を刺激し、下垂体からのバゾプレッシン遊離を介してラットの昇圧と抗利尿をひきおこすことを示した(神谷)。 2.心血管系:イヌ側頭動脈をニコチンで刺激した際、アドレナリン作動神経刺激による収縮と、NO神経刺激による拡張、プロスタサイクリン遊離を介する拡張がひきおこされるとの結論を得た(戸田)。平滑筋と内皮の単離細胞において、NO合成酵素の誘導の機序が異なることを示した(加藤)。ラット胎児脳から得られたアストログリア細胞において、エンドセリン受容体(ET_B)のdown regulationを観察し、神経の損傷修復との関連を考えさせるデータを得た(後藤)。冠血流遮断後再潅流時の心筋障害にリゾフォスファチジルコリンが蓄積するが、この物質の作用にナトリウムとカルシウムが関与することを示した(安孫子)。 3.平滑筋:ウサギ大動脈を用いて、βハロエチルアミン化合物がα_<1B>受容体を不活性化するのにGTPを要することから、受容体の識別にG-蛋白が関与すると結論した(高柳)。ラット腸管から抽出したmRNAで卵母細胞に発現した血管作動性腸管収縮物質受容体の脱感作に、プロテインキナーゼCの関与することを示した(谷山)。

Research Products
(24 results)

All Other

All Publications (24 results)

[Publications] Toda,N.,et al.: "Cerebroarterial relaxations mediated by nitric oxide derived…" Journal of Vascular Research. 30. 61-67 (1993)
[Publications] Okamura,T.et al.: "Neurogenic and non-neurogenic relaxations caused by nicotine in…" Journal of Pharmacology and Experimental Therapeutics. 266. 1416-1421 (1993)
[Publications] Kitamura,Y.et al.: "Nitric oxide-mediated retinal arteriolar and arterial dilatation…" Investigative Ophthalmology and Visual Science. 34. 2859-2865 (1993)
[Publications] Kuriyama,K.et al.: "Structure and function of cerebral GABA_A and GABA_B receptors." Neuroscience Research. 17. 91-99 (1993)
[Publications] Nakayasu,H.et al.: "Immunoaffinity purification and characterrization of…" Journal of Biological Chemistry. 268. 8658-8664 (1993)
[Publications] Hirouchi,M.et al.: "Alteration of GABA_A receptor α_1-subunit mRNA in mouse brain…" European Journal of Pharmacology-Molecular Pharmacology Section. 247. 127-130 (1993)
[Publications] Momiyama,T.et al.: "Enhancement of D_2 receptor agonist-induced inhibition by D_1…" British Journal of Pharmacology. 110. 713-718 (1993)
[Publications] Tamura,Y.et al.: "Ifenprodil prevents glutamate cytotoxicity via polyamine modul…" Journal of Pharmacology and Experimental Therapeutics. 265. 1017-1025 (1993)
[Publications] Matsumoto,M.et al.: "Mu-Opioid receptors modulate noradrenaline release from the rat…" Brain Research. (in press). (1993)
[Publications] Marumo,T.et al.: "Nitric oxide synthase mRNA in endothelial cells:synergistic…" Japanese Journal of Pharmacology. 63. 327-334 (1993)
[Publications] Shintani,F.et al.: "Interleukin-1 β augments release of norepinephrine,domapnie and…" Journal of Neuroscience. 13. 3574-3581 (1993)
[Publications] Hama,H.et al.: "Action of endothelin-1 on rat astrocytes through the ET_B……" Biochemical Biophysical Research Communication. 186. 355-362 (1993)
[Publications] Hama,H.et al.: "A possible role of endothelin-1 in brain damage induced by…" Journal of Clinical Investigation. (in press). (1993)
[Publications] Saigo,A.et al.: "Central administration of senktide,a tachykinin NK-3 agonist,…" Neuroscience Letter. 159. 187-190 (1993)
[Publications] Takano,Y.et al.: "The mechanism of central pressor actions of tachykinin NK-3…" Regulatory Peptides. 46. 360-363 (1993)
[Publications] Yazawa,K.and Abiko,Y.: "Modulation by histamine of the delayed outward potassium……" British Journal of Pharmacology. 109. 142-147 (1993)
[Publications] Ehsanul Hoque A.N.et al.: "Cardioprotective effect of d-propranolol in ischemic-reperfused…" European Journal of Pharmacology. 236. 269-277 (1993)
[Publications] Hara,A.et al.: "Lidocaine attenuates both mechanical and metabolic changes…" American Journal of Physiology. 265. H1478-H1485 (1993)
[Publications] Satoh,M.et al.: "Chloroethylclonidine discriminates between α_<1A>-and α_<1B>-……" Japanese Journal of Pharmacology. 63. 1-8 (1993)
[Publications] Kokubu,N.et al.: "Contractile responses and calcium movements induced by α_1-……" General Pharmacology. 24. 1541-1545 (1993)
[Publications] Taniyama,K.et al.: "Involvement of cholinergic neuron in intestinal contraction by…" European Journal of Pharmacology. 235. 149-151 (1993)
[Publications] Kan,S.et al.: "Specific receptor for vasoactive intestinal contractor in……" European Journal of Pharmacology. (in press). (1994)
[Publications] Yoshimura,M.et al.: "Functional expression of specific receptors for vasoactive……" British Journal of Pharmacology. (in press). (1994)
[Publications] Toda,N.and Okamura,T.: "The Regulation of Cerebral Blood Flow" CRC Press, 13 (1993)

1993 Fiscal Year Annual Research Report

薬物受容体の機能とその調節

Principal Investigator

戸田 昇 滋賀医科大学, 医学部, 教授 (50025590)

Research Products

[Publications] Toda,N.,et al.: "Cerebroarterial relaxations mediated by nitric oxide derived…" Journal of Vascular Research. 30. 61-67 (1993)

[Publications] Okamura,T.et al.: "Neurogenic and non-neurogenic relaxations caused by nicotine in…" Journal of Pharmacology and Experimental Therapeutics. 266. 1416-1421 (1993)

[Publications] Kitamura,Y.et al.: "Nitric oxide-mediated retinal arteriolar and arterial dilatation…" Investigative Ophthalmology and Visual Science. 34. 2859-2865 (1993)

[Publications] Kuriyama,K.et al.: "Structure and function of cerebral GABA_A and GABA_B receptors." Neuroscience Research. 17. 91-99 (1993)

[Publications] Nakayasu,H.et al.: "Immunoaffinity purification and characterrization of…" Journal of Biological Chemistry. 268. 8658-8664 (1993)

[Publications] Hirouchi,M.et al.: "Alteration of GABA_A receptor α_1-subunit mRNA in mouse brain…" European Journal of Pharmacology-Molecular Pharmacology Section. 247. 127-130 (1993)

[Publications] Momiyama,T.et al.: "Enhancement of D_2 receptor agonist-induced inhibition by D_1…" British Journal of Pharmacology. 110. 713-718 (1993)

[Publications] Tamura,Y.et al.: "Ifenprodil prevents glutamate cytotoxicity via polyamine modul…" Journal of Pharmacology and Experimental Therapeutics. 265. 1017-1025 (1993)

[Publications] Matsumoto,M.et al.: "Mu-Opioid receptors modulate noradrenaline release from the rat…" Brain Research. (in press). (1993)

[Publications] Marumo,T.et al.: "Nitric oxide synthase mRNA in endothelial cells:synergistic…" Japanese Journal of Pharmacology. 63. 327-334 (1993)

[Publications] Shintani,F.et al.: "Interleukin-1 β augments release of norepinephrine,domapnie and…" Journal of Neuroscience. 13. 3574-3581 (1993)

[Publications] Hama,H.et al.: "Action of endothelin-1 on rat astrocytes through the ET_B……" Biochemical Biophysical Research Communication. 186. 355-362 (1993)

[Publications] Hama,H.et al.: "A possible role of endothelin-1 in brain damage induced by…" Journal of Clinical Investigation. (in press). (1993)

[Publications] Saigo,A.et al.: "Central administration of senktide,a tachykinin NK-3 agonist,…" Neuroscience Letter. 159. 187-190 (1993)

[Publications] Takano,Y.et al.: "The mechanism of central pressor actions of tachykinin NK-3…" Regulatory Peptides. 46. 360-363 (1993)

[Publications] Yazawa,K.and Abiko,Y.: "Modulation by histamine of the delayed outward potassium……" British Journal of Pharmacology. 109. 142-147 (1993)

[Publications] Ehsanul Hoque A.N.et al.: "Cardioprotective effect of d-propranolol in ischemic-reperfused…" European Journal of Pharmacology. 236. 269-277 (1993)

[Publications] Hara,A.et al.: "Lidocaine attenuates both mechanical and metabolic changes…" American Journal of Physiology. 265. H1478-H1485 (1993)

[Publications] Satoh,M.et al.: "Chloroethylclonidine discriminates between α_<1A>-and α_<1B>-……" Japanese Journal of Pharmacology. 63. 1-8 (1993)

[Publications] Kokubu,N.et al.: "Contractile responses and calcium movements induced by α_1-……" General Pharmacology. 24. 1541-1545 (1993)

[Publications] Taniyama,K.et al.: "Involvement of cholinergic neuron in intestinal contraction by…" European Journal of Pharmacology. 235. 149-151 (1993)

[Publications] Kan,S.et al.: "Specific receptor for vasoactive intestinal contractor in……" European Journal of Pharmacology. (in press). (1994)

[Publications] Yoshimura,M.et al.: "Functional expression of specific receptors for vasoactive……" British Journal of Pharmacology. (in press). (1994)

[Publications] Toda,N.and Okamura,T.: "The Regulation of Cerebral Blood Flow" CRC Press, 13 (1993)

戸田昇滋賀医科大学, 医学部, 教授 (50025590)