機能形態学教室
  Physiology & Anatomy
 

〒981-8558
宮城県仙台市青葉区小松島4-4-1
東北薬科大学 機能形態学教室
TEL 022-727-0125
FAX 022-727-0125
メンバー
教 授
櫻田 忍
准教授
溝口 広一、米澤 章彦
助 教
渡辺 千寿子
博士課程
2年;青木 祐太、今野 崇、高木 宏和、長岡 高史
修士課程
2年;大槻 明日奈、小田桐 遼、冨士原 翔太  1年;遠藤 有里子、菅原 陵
薬学6年
阿部 ゆう、榊 華奈、諏訪 智也、瀬川 茉里、田中彰次郎、神田 大輔、南雲 英樹、川又 瑛里、栗山珠美絵、花田 陽佳
薬学5年
足利 沙知、日下 未来、楠木 智教、平山 紗衣、船橋 兼紘、角田 理紀、佐々木香織、雪田 大樹、佐々木 駿、
佐藤 真琴、島貫 朋美、平  剛、高橋千奈美
生命4年 加藤 紗耶香、角 貴祐


研究内容
【新規鎮痛薬の開発】  モルヒネは、最強の鎮痛薬といわれているが、その一方で精神依存性、身体的依存性、耐性、呼吸抑制、便秘などの副作用を有し臨床上大きな問題となっている。近年、当研究室では精神依存性の無い強力な鎮痛薬の開発に成功した。現在、開発した鎮痛薬のデータをもとに、各副作用の発現機構を解明するとともに、副作用の全く無い鎮痛薬を開発すべく検討を行っている。
【μ オピオイド受容体の機能解析】
 モルヒネなどの麻薬性鎮痛薬は、μ オピオイド受容体に作用することにより強力な鎮痛作用を発現する。最近の分子生物学的研究により、この μ 受容体には30種類以上もの多様性(スプライスバリアント)が存在することが明らかとなった。しかし、この μ 受容体各種スプライスバリアントの薬理学的・生物学的特性は全く不明である。当研究室では μ 受容体スプライスバリアントを発現させた細胞を用いその薬理学的特性を解明するとともに、μ 受容体遺伝子エクソンに選択的なアンチセンスを用いて生理機能の解析を行っている。
【疼痛伝達機構の解明】
 疼痛(痛み)は、外的刺激に対する生体反応の一つであり、生体内の様々な物質によって伝達・制御されている。近年、当研究室ではヒスタミンも疼痛を伝達する生体内物質の一つであり、Nociceptin、GABA、Substance P、Glutamate といった生体内伝達物質を遊離する神経の連携によって疼痛が伝達・制御されていることを明らかにした。現在、未だ明らかとなっていない脊髄における疼痛制御機構を解明するとともに、神経障害性疼痛や癌性疼痛など、難治性疼痛の発症機構に関しても研究を行っている。
【動物モデルを用いた性機能の機能解析と治療薬評価】
 当研究室が確立した性機能の機能解析・評価モデルを用いて、様々な病態発症時における機能障害を解析するとともに、特異的な治療薬の探索・開発を行っている。


発表論文(2007〜)

2012年

Understanding anomalous adaptation in chronic pain for successful development of disease modifying drugs.

Giacinto Bagetta, Shinobu Sakurada

Curr. Opin. Pharmacol. 12

 

New vistas in opioid control of pain.

Hirokazu Mizoguchi, Chizuko Watanabe, Tsukasa Sakurada, Shinobu Sakurada

Curr. Opin. Pharmacol. 12

 

The involvement of the spinal release of glutamate and nitric oxide in peripheral noxious stimulation-induced pain-related behaviors -Study in mouse spinal microdialysis-.

Chizuko Watanabe, Hirokazu Mizoguchi, Giacinto Bagetta, Shinobu Sakurada

Neurosci. Lett. 515

 

mu-Opioid receptor-mediated alterations of allergen-induced immune responses of bronchial lymph node cells in a murine model of stress asthma.

Kaori Okuyama, Soichiro Ide, Shinobu Sakurada, Kazumasa Sasaki, Ichiro Sora, Gen Tamura, Yuichi Ohkawara, Motoaki Takayanagi, Isao Ohno

Allergol. Int. 61

 

Non-opioid nociceptive activity of human dynorphin mutants that cause neurodegenerative disorder spinocerebellar ataxia type 23.

Hiroyuki Watanabe, Hirokazu Mizoguchi, Dineke S Verbeek, Alexander Kuzmin, Fred Nyberg, Oleg Krishtal, Shinobu  Sakurada, Georgy Bakalkin

Peptides 35

 

ラット射精機能評価モデルを用いた副作用解析と治療薬探索.

米澤章彦、渡辺千寿子、溝口広一、河谷正仁、木村行雄、櫻田忍

自律神経  49


2011年

Intraplantar injection of bergamot essential oil induces peripheral antinociception mediated by opioid mechanism.

Tsukasa Sakurada, Hirokazu Mizoguchi, Hikari Kuwahata, Soh Katsuyama, Takaaki Komatsu, Luigi Antonio Morrone, Maria Tiziana Corasaniti, Giacinto Bagetta, Shinobu Sakurada

Pharmacol. Biochem. Behav. 97

 

Involvement of mouse μ-opioid receptor splice variants in the spinal antinociception induced by the dermorphin tetrapeptide analog amidino-TAPA.

Hirokazu Mizoguchi, Chizuko Watanabe, Takayuki Higashiya, Satoshi Takeda, Kaori Moriyama, Akihiko Yonezawa, Takumi Sato, Takaaki Komatsu, Tsukasa Sakurada, Shinobu Sakurada

Eur. J. Pharmacol. 651

 

Involvement of glial cells in the nociceptive behaviors induced by a high-dose of histamine administered intrathecally.

Hirokazu Mizoguchi, Takaaki Komatsu, Yoko Iwata, Chizuko Watanabe, Hiroyuki Watanabe, Toru Orito, Soh Katsuyama, Akihiko Yonezawa, Kenji Onodera, Tsukasa Sakurada, Sakurada Sakurada

Eur. J. Pharmacol. 653

 

Dermorphin tetrapeptide analogs as potent and long-lasting analgesics with pharmacological profiles distinct from morphine.

Hirokazu Mizoguchi, Giacinto Bagetta, Tsukasa Sakurada, Shinobu Sakurada

Peptides 32

 

Partial involvement of NMDA receptors and glial cells in the nociceptive behaviors induced by intrathecally administered histamine.

Hirokazu Mizoguchi, Takaaki Komatsu, Yoko Iwata, Chizuko Watanabe, Hiroyuki Watanabe, Toru Orito, Soh Katsuyama, Akihiko Yonezawa, Kenji Onodera, Tsukasa Sakurada, Shinobu Sakurada

Neurosci. Lett. 495

 

Inhibition of ERK phosphorylation by substance P N-terminal fragment decreases capsaicin-induced nociceptive response.

Takaaki Komatsu, Hirokazu Mizoguchi, Mika Sasaki, Chikai Sakurada, Minoru Tsuzuki, Shinobu  Sakurada, Tsukasa Sakurada

Neuropharmacology 61

 

Antinociceptive effects of spinally administered nociceptin/orphanin FQ and its N-terminal fragments on capsaicin-induced nociception.

Soh Katsuyama, Hirokazu Mizoguchi, Takaaki Komatsu, Chikai Sakurada, Minoru Tsuzuki, Shinobu  Sakurada, Tsukasa Sakurada

Peptides 32

 

2010年

The involvement of m-opioid receptors in the central nervous system in the worsening of allergic airway inflammation by psychological stress in mice.

Kaori Okuyama, Kana Wada, Shinobu Sakurada, Hirokazu Mizoguchi, Hiroshi Komatsu, Ichiro Sora, Gen  Tamura, Yuichi Ohkawara, Motoaki Takayanagi, Isao Ohno

Int. Arch. Allergy Immunol. 152

 

Neuropharmacology of the essential oil of bergamot.

Giacinto Bagetta, Luigi Antonio Morrone,  Laura Rombolà, Diana Amantea, Rossella Russo, Laura Berliocchi, Shinobu Sakurada, Tsukasa Sakurada, Domenicantonio Rotiroti, Maria Tiziana Corasaniti

Fitoterapia 81

 

Characterization of intrathecally administered hemokinin-1-induced nociceptive behaviors in mice.

Chizuko Watanabe, Hirokazu Mizoguchi, Akihiko Yonezawa, Shinobu Sakurada

Peptides 31

 

Lack of a rewarding effect and a locomotor-enhancing effect of the selective μ-opioid receptor agonist amidino-TAPA.

Hirokazu Mizoguchi, Chizuko Watanabe, Shin Osada, Maya Yoshioka, Yuta Aoki, Sanae Natsui, Akihiko Yonezawa, Shu-ichi Kanno, Masaaki Ishikawa, Tsukasa Sakurada, Shinobu Sakurada

Psychopharmacology 212

 

The cannabinoid 1 receptor antagonist AM251 produces nocifensive behavior via activation of ERK signaling pathway.

Soh Katsuyama, Hirokazu Mizoguchi, Takaaki Komatsu, Kohshi Nagaoka, Shinobu Sakurada, Tsukasa Sakurada

Neuropharmacology 59

 

2009年

Effects of insulin replacement on ejaculatory dysfunction in streptozotocin-induced diabetic rats.

Akihiko Yonezawa, Manabu Ebiko, Masaru Yoshizumi, Shin-nosuke Ise, Chizuko Watanabe, Hirokazu Mizoguchi, Masahiro Iwasaki, Yukio Kimura, Shinobu Sakurada

Int. J. Urol. 16

 

Synergistic actions of apomorphine and m-chlorophenylpiperazine on ejaculation, but not penile erection in rats.

Akihiko Yonezawa, Masaru Yoshizumi, Shin-Nosuke Ise, Chizuko Watanabe, Hirokazu Mizoguchi, Katsuo Furukawa, Hiromichi Tsuru, Yukio Kimura, Masahito Kawatani, Shinobu Sakurada

Biomed. Res. 30

 

Intrathecal substance P augments morphine-induced antinociception: possible relevance in the production of substance P N-terminal fragments.

Takaaki Komatsu, Mika Sasaki, Kengo Sanai, Hikari Kuwahata, Chikai Sakurada, Minoru Tsuzuki, Yoko  Iwata, Shinobu Sakurada, Tsukasa Sakurada

Peptides 30

 

Spinal ERK activation via NO-cGMP pathway contributes to nociceptive behavior induced by morphine-3-glucuronide.

Takaaki Komatsu, Shinobu Sakurada, Kazuhiro Kohno, Hideo Shiohira, Soh Katsuyama, Chikai Sakurada, Minoru Tsuzuki, Tsukasa Sakurada

Biochem. Pharmacol. 78

 

Nociceptive behavior induced by the endogenous opioid peptides dynorphins in uninjured mice: evidence with intrathecal N-ethylmaleimide inhibiting dynorphin degradation.

Koichi Tan-No, Hiroaki Takahashi, Osamu Nakagawasai, Fukie Niijima, Shinobu Sakurada, Georgy Bakalkin, Lars Terenius, Takeshi Tadano

Int. Rev. Neurobiol. 85

 

Mechanism of allodynia evoked by intrathecal morphine-3-glucuronide in mice.

Takaaki Komatsu, Shinobu Sakurada, Soh Katsuyama, Kengo Sanai, Tsukasa Sakurada

Int. Rev. Neurobiol. 85

 

(-)-Linalool attenuates allodynia in neuropathic pain induced by spinal nerve ligation in c57/bl6 mice.

Laura Berliocchi, Rossella Russo, Alessandra Levato, Vicenza Fratto, Giacinto Bagetta, Shinobu Sakurada, Tsukasa Sakurada, Nicola Biagio Mercuri, Maria Tiziana Corasaniti

Int. Rev. Neurobiol. 85

 

Intraplantar injection of bergamot essential oil into the mouse hindpaw: effects on capsaicin-induced nociceptive behaviors.

Tsukasa Sakurada, Hikari Kuwahata, Soh Katsuyama, Takaaki Komatsu, Luigi Antonio Morrone, Maria Tiziana Corasaniti, Giacinto Bagetta, Shinobu Sakurada

Int. Rev. Neurobiol. 85

 

New therapy for neuropathic pain.

Hirokazu Mizoguchi, Chizuko Watanabe, Akihiko Yonezawa, Shinobu Sakurada

Int. Rev. Neurobiol. 85

 

Effects of systemic administration of the essential oil of bergamot (BEO) on gross behaviour and EEG power spectra recorded from the rat hippocampus and cerebral cortex.

Laura Rombolà, Maria Tiziana Corasaniti, Domenicantonio Rotiroti, Cristina Tassorelli, Shinobu Sakurada, Giacinto Bagetta, Luigi Antonio Morrone

Funct. Neurol. 24

2008年

Ejaculatory response induced by a 5-HT2 receptor agonist m-CPP in rats: Differential roles of 5-HT2 receptor subtypes.

Akihiko Yonezawa, Masaru Yoshizumi, Manabu Ebiko, Shin-nosuke Ise, Chizuko Watanabe, Hirokazu Mizoguchi, Yukio Kimura, Shinobu Sakurada

Pharmacol. Biochem. Behav. 88

 

Intrathecal high-dose histamine induces spinally-mediated behavioral responses through a polyamine site of NMDA receptors.

Chizuko Watanabe, Toru Orito, Hiroyuki Watanabe, Hirokazu Mizoguchi, Akihiko Yonezawa, Kazuhiko Yanai, Jalal I. Mobarakeh, Kenji Onodera, Tsukasa Sakurada, Shinobu Sakurada

Eur. J. Pharmacol. 581

 

Possible involvement of dynorphin A release via μ1-opioid receptor on supraspinal antinociception of endomorphin-2.

Shinobu Sakurada, Toshiki Sawai, Hirokazu Mizoguchi, Hiroyuki Watanabe, Chizuko Watanabe, Akihiko Yonezawa, Masaya Morimoto, Takumi Sato, Takaaki Komatsu, Tsukasa Sakurada

Peptides 29

 

17Beta-estradiol prevents retinal ganglion cell loss induced by acute rise of intraocular pressure in rat.

Rossella Russo, Federica Cavaliere, Chizuko Watanabe, Carlo Nucci, Giacinto Bagetta,  Maria Tiziana Corasaniti, Shinobu Sakurada, Luigi Antonio Morrone

Prog. Brain Res. 173

 

モルヒネー3ーグルクロニドの脊髄内投与に伴うアロディニアの発現機構の解析.

小松生明、櫻田忍、櫻田司

Anesthesia 10

2007年

The distinctive effects of acute and chronic psychological stress on airway inflammation in a murine model of allergic asthma.

Kaori Okuyama, Keiko Ohwada, Shinobu Sakurada, Naoko Sato, Ichiro Sora, Gen Tamura, Motoaki Takayanagi, Isao Ohno

Allergol. Int. 56

 

Possible involvement of endogenous nociceptin/orphanin FQ in the pain-related behavioral responses induced by its own metabolite, nociceptin/orphanin FQ(14-17).

Hiroyuki Watanabe, Hirokazu Mizoguchi, Toru Orito, Soh Katsuyama, Akihiko Yonezawa, Chizuko  Watanabe, Tsukasa Sakurada, Shinobu Sakurada

Peptides 28

 

Involvement of endogenous opioid peptides in the antinociception induced by the novel dermorphin tetrapeptide analog amidino-TAPA.

Hirokazu Mizoguchi, Chizuko Watanabe, Hiroyuki Watanabe, Kaori Moriyama, Bunsei Sato, Keiko Ohwada, Akihiko Yonezawa, Tsukasa Sakurada, Shinobu Sakurada

Eur. J. Pharmacol. 560

 

Extracellular signal-regulated kinase (ERK) and nitric oxide synthase mediate intrathecal morphine-induced nociceptive behavior.

Takaaki Komatsu, Chikai Sakurada, Mika Sasaki, Kengo Sanai, Minoru Tsuzuki, Giacinto Bagetta, Shinobu Sakurada, Tsukasa Sakurada

Neuropharmacology 52

 

A Tyr-W-MIF-1 analog containing D-Pro2 discriminates among antinociception in mice mediated by different classes of μ-opioid receptors.

Daisuke Nakayama, Hiroyuki Watanabe, Chizuko Watanabe, Hirokazu Mizoguchi, Tsukasa Sakurada, Shinobu Sakurada

Eur. J. Pharmacol. 563

 

Intrathecal substance P (1-7) prevents morphine-evoked spontaneous pain behavior via spinal NMDA-NO cascade.

Tsukasa Sakurada, Takaaki Komatsu, Hikari Kuwahata, Chizuko Watanabe, Toru Orito, Chikai Sakurada, Minoru Tsuzuki, Shinobu Sakurada

Biochem. Pharmacol. 74

 

2006

Anti-inflammatory activity of 4,4'-dihydroxy-alpha-truxillic acid.

Yu-Ming Chi, Motoyuki Nakamura, Xi-Ying Zhao, Toyokichi Yoshizawa, Wen-Mei Yan, Fumio Hashimoto, Junei Kinjo, Toshihiro Nohara, Shinobu Sakurada

Biol. Pharm. Bull. 29

 

Antinociceptive activities of alpha-truxillic acid and beta-truxinic acid derivatives.

Yu-Ming Chi, Motoyuki Nakamura, Xi-Ying Zhao, Toyokichi Yoshizawa, Wen-Mei Yan, Fumio Hashimoto, Junei Kinjo, Toshihiro Nohara, Shinobu Sakurada

Biol. Pharm. Bull. 29

 

Possible involvement of dynorphin A (1-17) release via m1-opioid receptors in spinal antinociception by endomorphin-2.

Hirokazu Mizoguchi, Hiroyuki Watanabe, Takafumi Hayashi, Wataru Sakurada, Toshiki Sawai, Tsutomu Fujimura, Tsukasa Sakurada, Shinobu Sakurada

J. Pharmacol. Exp. Ther. 317

 

Differential inhibitory effects of on substance P- and capsaicin-induced nociceptive behavior in mice.

Hiroyuki Watanabe, Daisuke Nakayama, Masayuki Yuhki, Toshiki Sawai, Wataru Sakurada, Soh Katsuyama, Takafumi Hayashi, Chizuko Watanabe, Hirokazu Mizoguchi, Tsutomu Fujimura, Tsukasa Sakurada, Shinobu Sakurada

Peptides 27

 

Involvement of spinal m1-opioid receptors on the Tyr-D-Arg-Phe-sarcosin-induced antinociception.

Hirokazu Mizoguchi, Daisuke Nakayama, Hiroyuki Watanabe, Kanenori Ito, Wataru Sakurada, Toshiki Sawai, Tsutomu Fujimura, Takumi Sato, Tsukasa Sakurada, Shinobu Sakurada

Eur. J. Pharmacol. 540

 

Enhanced antinociceptive effects of morphine in histamine H2 receptor gene knockout mice.

Jalal Izadi Mobarakeh, Kazuhiro Takahashi, Shinobu Sakurada, Atsuo Kuramasu, Kazuhiko Yanai

Neuropharmacology 51

 

Contribution of spinal m1-opioid receptors and dynorphin B to the antinociception induced by Tyr-D-Arg-Phe-Sar.

Hirokazu Mizoguchi, Kanenori Ito, Hiroyuki Watanabe, Chizuko Watanabe, Soh Katsuyama, Tsutomu Fujimura, Tsukasa Sakurada, Shinobu Sakurada

Peptides 27

 

I 型糖尿病モデルラットにおける射精機能の変化

蛯子学、米澤章彦、善積克、伊勢慎之介、岩崎雅弘、木村行雄、櫻田 忍

日本性機能学会誌 21

 

Tyr-Pro-Trp-Gly-NH2Tyr-W-MIF-1analogであるTyr-D-Pro-Trp-Gly-NH2の抗侵害作用におけるμ オピオイド受容体の関与について

中山大助、渡邉廣行、藤村努、櫻田忍

東北薬科大学研究誌 53  

 



Copyright(C)2003 TOHOKU PHARMACEUTICAL UNIVERSITY All Rights Reservedd