1994 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_A受容体複合体に存在するベンゾジアゼパム受容体mRNAの発現はニコチン投与ないしアルコール依存成立時に増大することを明らかした(栗山)。ラットの腹側被蓋野に電気泳動的にドパミンD_1、D_2およびD_3アゴニストを投与し、これらサブタイプのドパミン受容体はいずれも抑制的機能を示すことを見出した(笹)。無麻酔ラットの脳を灌流し、海馬に適用した外因性および内因性セロトニンは5HT_3受容体を介して、神経からのノルアドレナリン遊離を抑制する可能性を示した(斉藤)。ラット海馬のバゾプレシン受容体は結合実験の成績よりV_<1a>受容体様性質を示し、副腎皮質ホルモンにより調節されている可能性が示唆されたが、mRNA発現実験では海馬にV_2受容体の存在が確かめられた(神谷)。 2.心血管系:ウシ大脳動脈の神経刺激による弛緩反応は伝達物質としてNOを遊離することによるが、この反応は共存するコリン作動神経由来のアセチルコリンによって前シナップス的に抑制されることを明らかにした(戸田)。培養平滑筋細胞への圧力刺激は、フォスフォリパーゼCを活性化し細胞内Ca^<2+>を増加して平滑筋の増殖をひきおこすことが示唆された(加藤)。分化した状態の培養アストロサイトのET-1による脱分化・増殖にプロテインキナーゼCを介さないMAPキナーゼの活性化が重要であることが示唆された(後藤)。ラットの心室筋細胞に各種β遮断薬を用いて検討した結果、リゾフォスファチジルコリンによるCa^<2+>上昇はβ遮断作用でも膜安定化作用(Na^+チャネル遮断作用)でも説明できないことがわかった(安孫子)。 3.平滑筋:ウサギ大動脈を用いて、α_1-受容体サブタイプを介した筋収縮におけるCa^<2+>-感受性増加機構には、H-7感受性キナーゼおよび定分子量G-蛋白質が関与していることを示した(高柳)。ラット腸管から抽出したmRNAでアフリカツメガエルの卵母細胞に発現させた受容体において、ニューロペプチドYとペプチドYY間の異種脱感作を認めた。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)。班会議において、各種受容体とそのサブタイプの効果発現へのかかわりが臓器において著しく異なる点に注目し討論を行った。

Research Products
(26 results)

All Other

All Publications (26 results)

[Publications] Ayajiki,K.et al.: "Nitric oxide mediates.and acetylcholine modulates.neurally・・・" Neuroscience. 54. 819-825 (1993)
[Publications] Okamura,T.et al.: "Inhibition by calmodulin antagonists of the neurgenic relaxation・・" European Journal of Pharmacology. 256. 79-83 (1994)
[Publications] Toda,N.et al.: "Human uterine arterial relaxation induced by nitroxidergic・・・" American Journal of Physiology. 266. H1446-H1450 (1994)
[Publications] Katsura,M.et al.: "Nicotine increases diazepam binding inhibitor(DBI) mRNA in・・・" Neuroscience Letters. 168. 1-4 (1994)
[Publications] Katsura,M.et al.: "Increase of diazepam binding inhibitor mRNA levels in the brains・・・" Journal of Pharmacology and Experimental Therapeutics. (in press). (1995)
[Publications] Amano,T.et al.: "Dopamine-induced protection of striatal neurons against kainate・・・" Brain Research. 655. 61-69 (1994)
[Publications] Toda,N.et al.: "Excitation by talipexole,a dopamine D_2 agonist,of caudate・・・" Life Sciences. 54. 957-966 (1994)
[Publications] Kashii,S.et al.: "Protective action of dopamine agonist glutamate neurotoxicity in・・・" Investigative Ophthalmology and Visual Science. 35. 685-695 (1994)
[Publications] Matsumoto,M.et al.: "Mu-Opioid receptors modulate noradrenaline release from the rat・・・" Brain Research. 636. 1-8 (1994)
[Publications] Matsumoto,M.et al.: "Modulation of norepinephrine release by serotonergic receptors in・・・" Journal of Phamracology and Experimental Therapeutics. 272(in press). (1995)
[Publications] Saito,R.et al.: "Vasopressin V1 receptor in rat hippocampus is regulated by・・・" Brain Research. 646. 170-174 (1994)
[Publications] Hirasawa,A.et al.: "Evidence for the existence of vaspopressin V2 receptor mRNA in・・・" Biochemical and Biophysical Research Communication. 205. 1702-1706 (1994)
[Publications] Hishikawa,K.et al.: "Pressure promotes DNA synthesis in rat cultured vascular・・・" Journal of Clinical Investigation. 93. 1975-1980 (1994)
[Publications] Hishikawa,K.et al.: "Pressure enhances endothelin-1 release from cultured human・・・" Hypertension. (in press). (1995)
[Publications] Sakurai,T.et al.: "Activin A stimulates mitogenesis in Swiss 3T3 fibroblasts・・・" Journal of Biological Chemistry. 269. 14118-14122 (1994)
[Publications] Yasuda,N.et al.: "Electrical field stimulation-generated free radicals cause loss・・・" British Journal of Pharmacology. 113. 21-28 (1994)
[Publications] Yorikane,R.et al.: "Possible involvement of endothelin-1 in cardiac hypertrophy." Arzneimittel-Forschung. 44. 412-415 (1994)
[Publications] 橋爪裕子他: "虚血心筋とリゾリン脂質" 環境制御. 15. 606-612 (1994)
[Publications] Hashizume H.et al.: "Effects of antiischemic drugs on veratridine-induced・・・" European Journal of Pharmacology. 271. 1-8 (1994)
[Publications] Kamigaki M.et al.: "Enhancement of ischemic myocardial metabolic derangement by・・・" Japanese Journal of Pharmacology. 65. 121-129 (1994)
[Publications] Shinkai,M.et al.: "Tachykinin receptors of the NK2 type involved in the acetylcholine・・" British Journal of Pharmacology. 108. 759-762 (1993)
[Publications] Satoh,M.et al.: "α_1-adrenoceptor subtypes mediating the regulation and modulation・・・" European Journal of Pharmacology. 265. 133-139 (1994)
[Publications] Shinkai,M.et al.: "Pre- and postjunctional actions of endothelin the rat iris・・・" Naunyn-Schmiederg's Archives of Pharmacology. 350. 63-67 (1994)
[Publications] Tsutsumi,K.et al.: "Enhanced expression of an endothelin ET_A receptor in capillaries・・・" Journal of Neurochemistry. 63. 2240-2247 (1994)
[Publications] Koizumi,S.et al.: "Two distinct pathways are involved in the endothelin-3-evoked・・・" European Journal of Pharmacology. 259. 195-201 (1994)
[Publications] Sawa,T.et al.: "Differential mechanism of peptide YY and neuropeptide Y in・・・" European Journal of Pharmacology. (in press).

1994 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] Ayajiki,K.et al.: "Nitric oxide mediates.and acetylcholine modulates.neurally・・・" Neuroscience. 54. 819-825 (1993)

[Publications] Okamura,T.et al.: "Inhibition by calmodulin antagonists of the neurgenic relaxation・・" European Journal of Pharmacology. 256. 79-83 (1994)

[Publications] Toda,N.et al.: "Human uterine arterial relaxation induced by nitroxidergic・・・" American Journal of Physiology. 266. H1446-H1450 (1994)

[Publications] Katsura,M.et al.: "Nicotine increases diazepam binding inhibitor(DBI) mRNA in・・・" Neuroscience Letters. 168. 1-4 (1994)

[Publications] Katsura,M.et al.: "Increase of diazepam binding inhibitor mRNA levels in the brains・・・" Journal of Pharmacology and Experimental Therapeutics. (in press). (1995)

[Publications] Amano,T.et al.: "Dopamine-induced protection of striatal neurons against kainate・・・" Brain Research. 655. 61-69 (1994)

[Publications] Toda,N.et al.: "Excitation by talipexole,a dopamine D_2 agonist,of caudate・・・" Life Sciences. 54. 957-966 (1994)

[Publications] Kashii,S.et al.: "Protective action of dopamine agonist glutamate neurotoxicity in・・・" Investigative Ophthalmology and Visual Science. 35. 685-695 (1994)

[Publications] Matsumoto,M.et al.: "Mu-Opioid receptors modulate noradrenaline release from the rat・・・" Brain Research. 636. 1-8 (1994)

[Publications] Matsumoto,M.et al.: "Modulation of norepinephrine release by serotonergic receptors in・・・" Journal of Phamracology and Experimental Therapeutics. 272(in press). (1995)

[Publications] Saito,R.et al.: "Vasopressin V1 receptor in rat hippocampus is regulated by・・・" Brain Research. 646. 170-174 (1994)

[Publications] Hirasawa,A.et al.: "Evidence for the existence of vaspopressin V2 receptor mRNA in・・・" Biochemical and Biophysical Research Communication. 205. 1702-1706 (1994)

[Publications] Hishikawa,K.et al.: "Pressure promotes DNA synthesis in rat cultured vascular・・・" Journal of Clinical Investigation. 93. 1975-1980 (1994)

[Publications] Hishikawa,K.et al.: "Pressure enhances endothelin-1 release from cultured human・・・" Hypertension. (in press). (1995)

[Publications] Sakurai,T.et al.: "Activin A stimulates mitogenesis in Swiss 3T3 fibroblasts・・・" Journal of Biological Chemistry. 269. 14118-14122 (1994)

[Publications] Yasuda,N.et al.: "Electrical field stimulation-generated free radicals cause loss・・・" British Journal of Pharmacology. 113. 21-28 (1994)

[Publications] Yorikane,R.et al.: "Possible involvement of endothelin-1 in cardiac hypertrophy." Arzneimittel-Forschung. 44. 412-415 (1994)

[Publications] 橋爪 裕子 他: "虚血心筋とリゾリン脂質" 環境制御. 15. 606-612 (1994)

[Publications] Hashizume H.et al.: "Effects of antiischemic drugs on veratridine-induced・・・" European Journal of Pharmacology. 271. 1-8 (1994)

[Publications] Kamigaki M.et al.: "Enhancement of ischemic myocardial metabolic derangement by・・・" Japanese Journal of Pharmacology. 65. 121-129 (1994)

[Publications] Shinkai,M.et al.: "Tachykinin receptors of the NK2 type involved in the acetylcholine・・" British Journal of Pharmacology. 108. 759-762 (1993)

[Publications] Satoh,M.et al.: "α_1-adrenoceptor subtypes mediating the regulation and modulation・・・" European Journal of Pharmacology. 265. 133-139 (1994)

[Publications] Shinkai,M.et al.: "Pre- and postjunctional actions of endothelin the rat iris・・・" Naunyn-Schmiederg's Archives of Pharmacology. 350. 63-67 (1994)

[Publications] Tsutsumi,K.et al.: "Enhanced expression of an endothelin ET_A receptor in capillaries・・・" Journal of Neurochemistry. 63. 2240-2247 (1994)

[Publications] Koizumi,S.et al.: "Two distinct pathways are involved in the endothelin-3-evoked・・・" European Journal of Pharmacology. 259. 195-201 (1994)

[Publications] Sawa,T.et al.: "Differential mechanism of peptide YY and neuropeptide Y in・・・" European Journal of Pharmacology. (in press).

戸田昇滋賀医科大学, 医学部, 教授 (50025590)

[Publications] 橋爪裕子他: "虚血心筋とリゾリン脂質" 環境制御. 15. 606-612 (1994)