教授 ： 柳原　延章 （医学博士）

北米神経科学会
日本薬理学会
日本循環器学会
日本薬学会
日本フードファクター学会

1)      CA生合成及び分泌の調節機序：特にチロシン水酸化酵素の蛋白質リン酸化酵素によるリン酸化と活性化

2)      精神疾患治療薬、麻酔薬等のノルエピネフリントランスポーターへの影響

3)      内分泌かく乱化学物質のCA神経系細胞への影響

4)      神経−内分泌−免疫連関の研究：特にCA神経系へ作用するリンパ球由来因子のファジイセットクローニング

5)      細胞膜エストロゲン受容体の分子薬理、生物学的検討

6)      CA神経系細胞の機能へ影響を及ぼす植物性由来物質の検索とその同定

カテコールアミン (CA) の研究は、一般に神経伝達物質の研究に多くの示唆を与え、またCAが関与する生理・病理（高血圧、循環器疾患、パーキンソン病及び精神神経疾患など）の理解にも重要であります。そこで、以下のCA研究を行なっています。

カテコールアミン、生合成、チロシン水酸化酵素、蛋白リン酸化酵素、
リンパ球由来因子、内分泌撹乱化学物質、植物性エストロゲン、細胞
膜エストロゲン受容体、生薬成分
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[文責 : 薬理学講座　 更新日：2006年 3月30日]

1.               Yanagihara N., Liu M., Toyohira Y., Tsutsui M., Ueno S., Shinohara Y., Takahashi K., Tanaka K. (2006) Stimulation of catecholamine synthesis through unique estrogen receptors in the bovine adrenomedullary plasma membrane by 17β-estradiol. BBRC, 339:548-553

2.               Yanagihara N., Toyohira Y., Ueno S. et al (2005) Stimulation of catecholamine synthesis by environmental estrogenic pollutants. Endocrinol. 146: 265-272

3.               Toyohira Y., Kubo T., Watanabe M., Uezono Y., Ueno S., Shinkai K., Tsutsui M., Izumi I., and Yanagihara N. (2005) Selective blockade of nicotinic acetylcholine receptors by pimobendan, a drug for the treatment of heart failure: reduction of catecholamine secretion and synthesis in adrenal medullary cells. Naunyn-Schimiedeberg’s Arch. of Pharmacology, 371:107-113

4.               Ueno S., Tsutsui M., Toyohira Y., Minami K., Yanagiara N. (2004) Sites of positive allosteric modulation by neurosteroids in ionotropic g-aminobutyric acid recptor subunits. FEBS Letters 566: 213-217

5.               Horiuchi M., Tsutsui M., Tasaki H., Morishita T., Suda O., Nakata S., Nihei S., Miyamoto M., Kouzuma R., Okazaki M., Yanagihara N., Adachi T., Nakashima Y. (2004)  Upregulation of vascular extracellular superoxide dismutase in patients with acute coromary syndromes. Arterioscler Thromb Vas Biol., 24: 106-111

6.               Suda O., Tsutsui M., Morishita T., Tasaki H., Ueno S., Nakata S., Tsujimoto T., Toyohira Y., Hayashida Y., Sasaguri Y., Ueta Y., Nakashima Y., Yanagihara N. (2004) Asymmetric dimethylargine produces vascular lesions in endotherial nitric oxide synthase-deficient mice: Involvement of rennin-angiotensin system and oxidative stress.  Arterioscler Thromb Vas Biol., 24: 1682-1688

7.               柳原延章、豊平由美子、上野　晋、筒井正人 (2003) 内分泌撹乱物質のカテコールアミン動態への影響. 脳の科学 25: 1149-1154

8.               Yanagihara N., Toyohira Y., Tanaka K. et al (2003) Disturbances in catecholamine synthesis, release and reuptake by xenoestrogens. J. UOEH. 25: 169-179

9.               Toyohira Y., Utsunomiya K., Ueno S., Minami K., Uezono Y., Yoshimura R., Tsutsui M., Izumi F.,  Yanagihara N. (2003) Inhibition of the norepinephrine transporter function in cultured bovine adrenal medullary cells by bisphenol A. Biochemical Pharmacology 65: 2049-2054

10.           Kawada Y., Ueno S., Asayama K., Tsutsui M., Utsunomiya K., Toyohira Y., Morisada N., Tanaka K.,  Shirahata A., Yanagihara N. (2003) Stimulation of catecholamine synthesis by orexin-A in bovine adrenal medullary cells throush orexin receptor1. Biochemical Pharmacology 66:141-147

11.           Tsutsui M., Ueno S., Toyohira Y., Yangihara N. (2002) Structure and function of nitric oxide synthases. Tanpakushitsu Kakusan Koso 47: 2024-2031

12.           Morishita T., Tsutsui M., Yanagihara N. et al. (2002) Vasculoprotective roles of neuronal nitric oxide synthase. FASEB J. 16: 1994-1996

13.           Koshimizu T.-A., Ueno S., Yanagihara N. et al. (2002) Heteromultimerization modulates P2X receptor functions through participating extracellular and C-terminal subdomains. J. Biol. Chem. 277: 46891-46899

14.           Shiraishi M., Shibuya I., Yanagihara N. et al. (2002) A neurosteroid anesthetic, alphaxalone, inhibits nicotinic acetylcholine receptors in cultured bovine adrenal chromaffin cells. Anest. Analg. 95: 900-906

15.           Hiwatashi Y., Kurahashi Y., Yanagihara N. et al. (2002) Glucocorticoid inhibits expression of V-1, a catecholamine biosynthesis regulatory protein, in cultured adrenal medullary cells. FEBS Lett. 528: 166-170

16.           Suda O., Tsutsui M., Morishita T. et al. (2002) Long-term treatment with Nω-nitro-L-arginine methyl ester causes arteriosclerotic coronary lesions in endothelial nitric oxide synthase-deficient mice. Circulation 106:1729-1735

17.           Kajiwara K., Yanagita T., Yanagihara N. (2002) Differential effects of short and prolonged exposure to carvedilol on voltage-dependent Na+ channels in cultured bovine adrenal medullary cells. J. Pharmacol. Exp.Ther.  302: 212-218

18.           Hara K., Minami K., Yanagihara N. (2002) Up-regulation of noradrenaline transporter in response to prolonged exposure to ketamine. Naunyn-Schmiedeberg's Arch.Pharmacol. 365: 406-412

19.           Shiraishi M., Minami K., Yanagihara N. et al. (2002) Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in Xenopus oocytes expressing α7 receptors. Br. J. Pharmacol. 136: 207-216

20.           Ueno S., Minami K., Yanagiohara N. (2001) Structure and function of GABAA receptors: recent studies by site-directed mutagenesis. Tanpakushitsu Kakusan Koso 46: 2042-2051

21.           Shiraishi M., Minami K., Yanagihara N. et al. (2001) Inhibition by tramadol of muscarinic receptor-induced responses in cultured adrenal medullary cells and in Xenopus laevis oocytes expressing cloned M1 receptors. J. Pharmacol. Exp. Ther. 299: 255-260

22.           Yoshimura R., Yanagihara N., Hara K. et al. (2001) Dual phases of functional change in norepinephrine transporter in cultured bovine adrenal medullary cells bylong-termtreatment with clozapine. J. Neurochem. 77: 1018-1026

23.           Utsunomiya K., Yanagihara N., Tachikawa E. et al. (2001) Stimulation of catecholamine synthesis in cultured bovine adrenal medullary cells by leptin. J. Neurochem. 76: 926-934

24.           Yanagihara N., Utsunomiya K., Cheah TB. et al (2000) Characterization and functional role of leptin receptor in bovine adrenal medullary cells. Biochem. Pharmacol. 59: 1141-1145

25.           Hara K., Yanagihara N., Minami K. (2000) Dual effects of intravenous anesthetics on the function of norepinephrine transporters. Anesthesiology 93:1329-1335

26.           Yoshimura R., Yanagihara N., Hara K. et al. (2000) Inhibitory effects of clozapine and other antipsychotic drugs on noradrenaline transporter in cultured bovine adrenal medullary cells. Psychopharmacology 149: 17-23

27.           Yanagihara N., Tsutsui M., Miyamoto E. et al (1998) Short-termregulation of catecholamine synthesis by Ca2+/calmodulin-dependent protein kinase II. pp243-247, The Adrenal Chromaffin Cell, ed. by Kanno, T. et al., Hokkaido University Press

28.           Yanagihara N., Izumi F., Miyamoto E. et al (1998) Factorsaffecting adrenal medullary catecholamine biosynthesis and release. Carecholamines Bridging Basic Science with Clinical Medicine, ed. by Goldstein D., Advances in Pharmacology, 42: 18-21, Academic Press, New York

29.           Yanagihara N., Hara K., Kajiwara K. et al (1998) Stimulatory effect of lymphocyte-derived factor on catecholamine efflux from cultured bovine adrenal medullary cells. Neurosci. Lett. 243: 25-28

30.           柳原延章、豊平由美子、上園保仁、上野　晋、泉　太 (1998) 副腎髄質クロマフィン細胞におけるCa2+情報伝達機序. 蛋白質核酸酵素 43: 1777-1783

31.           Yanagihara N., Oishi Y., Yamamoto H., et al (1996) Phosphorylation of chromogranin A and catecholamine secretion stimulated by elevation of intracellular Ca2+ in cultured bovine adrenal medullary cells. J. Biol. Chem. 271:17463-17468

32.           Yanagihara N., Minami K., Shirakawa F. et al (1994) Stimulatory effect of IL-1 on catecholamine secretion from bovine adrenal medullary cells. Biochem. Biopysic. Res. Commun. 198: 81-87

33.           Yanagihara N., Toyohira Y., Yamamoto H. et al (1994) Occurrence and activation of Ca2+/Calmodulin-dependent protein kinase II and its endogenous substrates in bovine adenal medullary cells. Mol. Pharmacol. 46: 423-430

34.           柳原延章 (1993) イオンチャネルとセカンドメッセンジャー：カムキナーゼによる修飾、「イオンチャネル：１」東田陽博、メジカルビュー社 （東京）：202-211

35.           柳原延章 (1993) イオンチャネルとセカンドメッセンジャー：A キナーゼによる修飾、「イオンチャネル：１」東田陽博、メジカルビュー社（東京）：192-201

36.           Yanagihara N., Okazaki M., Terao T. et al (1991) Stimulatory effects of brain natriuretic peptide on cyclic GMP accumulation and tyrosine hydroxylase activity in cultured bovine adrenal medullary cells. Naunyn-Schmiedeberg’s Arch. of Pharmacol. 343: 289-295

37.           Yanagihara N., Tachikawa E., Izumi F. et al (1991) Staurosporine: An effective inhibitor for Ca2+/Calmodulin-dependent protein kinase II. J. Neurochem. 56: 294-298

38.           Yanagihara N., Yokota K., Kobayashi H. et al (1990) Sodium/proton exchange in　cultured bovine adrenal medullary cells. J. Neurochem. 54: 1626-1631

39.           Yanagihara N., Yokota K., Wada A. et al (1987) Intracellular pH and catecholamine synthesis in cultured bovine adrenal medullary cells: Effect of extracellular Na+ removal. J.Neurochem. 49: 1740-1746

40.           Yanagihara N., Uezono Y., Koda Y. et al (1987) Activation of tyrosine hydroxylase by micromolar concentrations of calcium in digitonin-permeabilized adrenal medullary cells. Biochem. Biophys. Res. Commun. 146: 530-536

41.           Yanagihara N., Wada A., Izumi F (1987) Effects of a2-adrenergic agonists on carbachol-stimulated catecholamine synthesis in cultured bovine adrenal medullary cells. Biochem. Pharmacol. 36: 3823-3828

42.           Yanagihara N., Tank A W., Langan T A. et al (1986) Enhanced phosphorylation of tyrosine hydroxylase at more than one site is induced by 56mMK+ in rat pheochromocytoma PC12 cells in culture. J. Neurochem. 46: 562-568

43.           Yanagihara N., Tank A W., Weiner N. (1984) Relationship between activation and phosphorylation of tyrosine hydroxylase by 56mMK+ in PC12 cells in culture. Mol. Pharmacol. 26: 141-147

44.           Yanagihara N., Isosaki M., Ohuchi T. et al (1979) Muscarnic receptor-mediated increase in cyclic GMP level in isolated bovine adrenal medullary cells. FEBS Lett 105: 296-298