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the role of mu-opioid receptor subtypes on antinociception of mu-opioid receptor agonists

Research Project

Project/Area Number 12672220
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionTohoku Parmaceutical University

Principal Investigator

SAKURADA Shinobu  Tohoku Pharmaceutical University, Department of Physiology and Anatomy, Professor, 薬学部, 教授 (30075816)

Project Period (FY) 2000 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsmu-opioid receptor antagonist / mu1-opioid receptor / mu2-opioid receptor / endomorphin-1 / endomorphin-2 / naloxonazine / β-funaltrexamine / D-Pro^2-endomorphins / D-Pro-endomorphin-1 / D-Pro-endomorphin-2 / DAMGO / μ opioid / 3-methoxynaltorexone
Research Abstract

At least two mti-oploid receptor subtypes have been proposed; mul-and mu2-opioid rceptor subtypes. β-funaltrexamine irreversibly antagonizes both mul-and mu2-oploid receptors, whereas naloxonazine selectively antagonizes the mul-oplold receptor. However, the selective mu2-opioid antagonist has not yet been found. We found that D-Pro^2-endomorphin-1 selectively blocked the antinociceptive effect of i.t. administered DAMGO, as well as endomorphin-1, whereas antln6ciceptlon of Tyr-D-Arg-Phe-p-AJa, or endomorphin-2 was InhibIted by co-administration of D-Pro but not D-Pro Theses results indicate that these rwo D-Pro^2-endomorphins may be a useful tool to dlscrimate between the antinociceptive effects of mul-and mu2-oploid receptor agonists.

Report

(5 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Shinobu Sakurada: "Synthesis and structure-activity relationships of an orally-available and long-acting analgesic peptide, α-amidino-Tyr-D-Arg-Phe-Me β Ala-OH (ADAMB)"J.Med.Chem.. 45. 5081-5089 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada: "Endomorphin analogues containing D-Pro^2 discriminate different μ-opioid receptor mediated antinociception in mice"Brit.J.Pharmacol.. 137. 1143-1146 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada: "D-Pro^2-andomorphin-1 and D-Pro^2-endomorphin-2, respectively, attenuate the antinociception induced by encomorphin-1 and endomorphin-2 given intrathecally in the mouse"J.Pharmacol.Exp.Ther.. 303. 874-879 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada: "Blood-brain barrier transport of a novel μ1-specific opioid peptide, H-Tyr-D-Arg-Phe-β-Ala-OH(TAPA)"J.Neurochem. 84. 1154-1161 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada: "Differential involvement of μ1-opioid receptor in dermorphin tetrapeptide analogues-induced antinociceptin"Eur.J.Pharmacol.. 486. 19-24 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tsukasa Sakurada, Masayuki Yuhki, Makoto Inoue, Chikai Sakurada, Koichi Tan-No, Masataka Obba, Kensuke Kisara, Shinobu Sakurada: "Opiold activity of sendide, a tachykinin NJC1 receptor antagonist"European Journal of Pharmacology. 369. 261-266 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada, James E.Zadina, Abba J.Kastin, Sou Katsuyama, Tsutomu Fujimura, Kimie Murayama, Masayuki Yuki, Hiroshi Ueda, Tsukasa Sakurada: "Differential involvement of μ-opioid receptor subtypes in endomorphin-1-and -2-induced antinociception"European Journal of Pharmacology. 372. 25-30 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] O.Nakagawasai, T.Tadano, K.Tan-No, F.Nuijinia, S.Sakurada, Y.Endo, K.Kisara: "Changes in β-Endorphin and Stress-Induced Analgesia in Mice After Exposure to Forced Walking Stress"Methods Find.ExClin.Pharmacol.. 21. 471-476 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukie Niijima.Koichi Tan-No, Akihisa Esashi, Osamu Nakagawasai, Takeshi Tadano, Norio Takahashi, Akihiko Yonezawa, Shinobu Sakurada, Kensuke Kisara: "Inhibitory effect of intracerebroventricularly-admninistered [D-Arg^2,β-Ala^4]-dermorphin (1-4) on gastrointestinal transit"Pepties. 21. 295-299 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada, Satoshi Takeda, Takumi Sato, Takafumi Hayashi, Masayuki Yuki, Motoharu Kutsuwa, Koichi Tan-No, Chikai Sakurada, Kensuke Kisara, Tsukasa Sakurada: "Selective antagonism by naloxonsaine of antinoclception by Tyr-D-Arg-Phe-p-AIa, a novel dermorphin analogue with high affinity at μ-opioid receptors"European Journal of Pharmacology. 395. 107-112 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada, Takafumi Hayashi, Masayuki Yuhki, Tsutomu Fujimura, Kimie Murayama, Akihiko Yonezawa, Chikai Sakurada, Mitsuhiro Takeshita, James E.Zadina, Abba I.Kastin, Taukasa Sakurada: "Differential antagonism of endomorphin-1 and endomorphin-2 spinal antinociception by naloxonazins and 3-mnethoxynaltrexone"BRAIN RESEARCH. 881. 1-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada, Takafumi Haysahi, Masayuki Yuhki, Tohru Onto, James E.Zadina, Abba I.Kastin, Tsutomu Fujimura, Kimie Murayama, Chikai Sakurada, Tsukasa Sakurada, Minoni Narita, Tsutomu Suzuki, Koichi Tan-no, Leon F.Tseng: "Differential antinociceptive effects induced by intrathecatly administered endomorphin-I and endomorpbin-2 in the mouse"European Journal of Pharmacology. 472. 203-210 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Tadashi Ogawa, Tetauhisa Miyamae, Toni Okayama, Masaki Hagiwara, Shinobu Sakurada, Tadanori Morikawa: "Structure-Activity Relationships (SAR) of [D-Arg Analogues, N-Amidino-Tyr-D-Arg-Phe-X"Chem.Pharm.Bull.. 50. 771-780 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Minoru Narita, Shinobu Sakurada: "Recent Advances In the Search for the μ-OpioidergiF System"Jpn.J.Pharmacol.. 89. 201-202 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada, Takafumi Hayashi, Masayuki Yuhki: "Differential Antinociceptive Effects Induced by Intrathecally. Admlnistered Endomorphin-1 and Endomorphin-2 in Mice"Jpn.J.Pharmacol. 90. 221-223 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada, Takafumi Hayashi, Masayuki Yuhki, Tsutomu Fujimura, Kimie Murayama, Akihiko Yonezawa, Oiikai Sakurada, Mitauhiro Takeshita, Takumi Sato, James B.Zadina, Abba J.Kastin, Tsukasa Sakurada: "Differential antagonism of endomorphin-1 and endomorphin-2 supraspinal antinociception by naloxonazine and 3-methylnaltzexone"Peptides. 23. 895-901 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuei-Chung Hung, Hsiang-En Wu, Hirokazu Mizoguchi, Shinobu sakurada, Torii Okaysma, Tsutomu Fujimura, Kimie Murayama, Tsukasa Sakurada, James M.Fujimoto, Leon F.Tseng: "D-Pro^2-Endomorphin-1 and D-Pro^2-Endomorphin-2 Respectively, Attenuate the Antinociception Induced by Endomorphln-1 and Endomorphin-2 Given Intrathecatly in the Mouse"J.Pharmacol.ExTher.. 303. 874-879 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada, Hiroyuki Watanabe, Takafumi Hayashi, Masayuki Yuhki, Tsutomu Fujimura, Kimie Maruyama, Chikai Sakurada, Tsukasa Sakurada: "Endomorphin analogues containing D-Pro^2 different μ-opioid receptor mediated antinociception in mice"British Journal Pharmacology. 137. 1143-1146 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshiharu Deguchi, Yusaku Miyakawa, Shinobu Sakurada, Yu Naito, Kazuhiro Morimoto, Sumio Ohtsuki, Ken-ichi Hosoya, Tetsuya Terasaki: "Blood-brain barrier transport of a novel 1&,-specific opioid peptide, H-Tyr-D-Arg-Phe-β-Ala-0H (TAPA)"Journal of Meurochemistry. 84. 1154-1161 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chikai Sakurada, Shinobu Sakurada, Takafumi Hayashi, Sou Katsuyama, Koichi Tan-No, Tsukasa Sakurada: "Degradation of endomorphin-2 at the supraspinal level in mice is initiated by dipeptidyl peptidase IV: an in vitro and in vivo study"Biochemical Pharmacology. 66. 653-661 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirokazu Mizoguchi, Masayuki Yuhki, Hiroyuki Watanabe, Takafumi Hayashi, Chikai Sakurada, Akihiko Yonezawa, Tsukasa Sakurada, Shinobu Sakurada: "Differential involvement of μ_1 receptor on dermorphin tetrapeptide analogues-induced antinociception"European Journal of Pharmacology. 486. 19-24 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinobu Sakurada: "Synthesis and structure-activity relationships of an orally-available and long-acting analgesic peptide, α- amidino-Tyr-D-Arg-Phe-Me β Ala-OH (ADAMB)"J.Med.Chem.. 5081-5089 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shinobu Sakurada: "Endomorphin analogues containing D-Pro^2 discriminate different μ-opioid receptor mediated antinociception in mice"Brit.J.Pharmacol. 1143-1146 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shinobu Sakurada: "Differential antagonism of endomorphin-1 and endmorphin-2 supraspinal antinociception by naloxonazine and 3-methylnaltrexone"Peptides. 895-901 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shinobu Sakurada: "D-Pro^2-endomorphin-1 and D-Pro^2-endmorphin-2, respectively, attenuate the antinociception induced by endomorphin-1 and endomorphin-2 given intrathecally in the mouse"J.Pharmacol.Exp.Ther. 874-879 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shinobu Sakurada: "Blood-brain barrier transport of a novel μ1-specific opioid peptide, H-Tyr-D-Arg-Phe-β- Ala-OH(TAPA)"J.Neurochem. 1154-1161 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shinobu Sakurada: "Differential involvement of μ1-opioid receptor in dermorphin tetrapeptide analogues-induced antinociception"Eur.J.Pharmacol. 19-24 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shinobu Sakurada: "Synthesis and structure-activity relationships of an orally-available and long-acting analgesic peptide, N^α-amidino-Tyr-D-Arg-Phe-MeβAla-OH (ADAMB)"J. Med. Chem. 45. 5081-5089 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinobu Sakurada: "Endomorphin analogues containing D-Pro^2 discriminate different μ-opiod receptor mediated antinociception in mice"Brit. J. Pharmacol. 137. 1143-1146 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinobu Sakurada: "Structure-activity relationships (SAR) of [D-Arg^2]dermorphin(1-4) analogues, N^α-amidino-Tyr-D-Arg-Phe-X"Chem. Pharm. Bull. 50. 771-780 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinobu Sakurada: "Differential antagonism of endomorphin-1 and endmorphin-2 supraspinal antinociception by naloxonazine and 3-methylnaltrexone"Peptides. 23. 895-901 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinobu Sakurada: "D-Pro^2-endomorphin-1 and D-Pro^2-endomorphin-2, respectively, attenuate the anitinociception induced by endomorphin-1 and endomorphin-2 given intrathecally in the mouse"J. Pharmacol. Exp. Ther. 303. 874-879 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinobu Sakurada: "Blood-brain barrier transport of a novel μ_1-specific opioid peptide, H-Tyr-D-Arg-Phe-β-ala-OH (TAPA)"J. Neurochem. 84. 1154-1161 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takumi Sato: "Contribution of spinal μ1-opioid receptors to morphine-induced antinociception."Eur. J. Pharmacol. 369. 183-187 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinobu Sakurada: "Differential involvement of μ-opioidreceptor subtype in endomorphin-1 and -2-induced antinociception."Eur. J. Pharmacol. 372. 25-30 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinobu Sakurada: "Selective antagonism by naloxonazine of antinociception by Tyr-D-Arg-Phe-β-Ala, novel dermorphin analogue with high affinity at μ-opioidreceptors."Eur. J. Pharmacol. 395. 107-112 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinobu Sakurada: "Differential antagonism of endomorphin-1 and endomorphin-2 spinal antinociception by naloxonazine and 3-methoxynaltrexone."Brain Research. 881. 1-8 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinobu Sakurada: "Differential antinociceptive effects induced by intrathecally dministered endomorphin-1 and endomorphin-2"Eur. J. Pharmacol. 427. 203-210 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takumi Sato: "Contribution of spinal μ1-opioid receptors to morphine-induced antinociception."Eur.J.Pharmacol. 369. 183-187 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinobu Sakurada: "Differential involvement of μ-opioidreceptor subtype in endomorphin-1 and 2-induced antinociception."Eur.J.Pharmacol.. 372. 25-30 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinobu Sakurada: "Selective antagonism by naloxonazine of antinociception by Tyr-D-Arg-Phe-β-Ala, novel dermorphin analogue with high affinity at μ-opioidreceptors."Eur.J.Pharmacol. 395. 107-112 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinobu Sakurada: "Differential antagonism of endomorphin-1 and endomorphin-2 spinal antinociception by naloxonazine and 3-methoxynaltrexone."Brain Research. 881. 1-8 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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