Spinorphin, an endogeneous inhibitor of enkephalin-degrading enzymes, protentiates leu-enkephalin-induced anti-allodynic and antinociceptive effects in mice

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  • Honda Motoko
    Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University
  • Okutsu Hiroko
    Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo
  • Matsuura Tomoyuki
    Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo
  • Miyagi Tomohiro
    Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo
  • Yamamoto Yukio
    Department of Molecular Oncology, The Tokyo Metropolitan Institute of Medical Science
  • Hazato Tadahiro
    Department of Molecular Oncology, The Tokyo Metropolitan Institute of Medical Science
  • Ono Hideki
    Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University

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タイトル別名
  • Spinorphin, an Endogenous Inhibitor of Enkephalin-Degrading Enzymes, Potentiates Leu-Enkephalin-Induced Anti-allodynic and Antinociceptive Effects in Mice.

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抄録

Spinorphin (LVVYPWT) has been isolated from the bovine spinal cord as an endogenous inhibitor of enkephalin-degrading enzymes. It has been reported that spinorphin has an antinociceptive effect, inhibitory effect on contraction of smooth muscle and anti-inflammatory effect. In the present study, the effects of leu-enkephalin and spinorphin on allodynia and mechanical and thermal nociceptions were examined in vivo using mice. Intrathecal (i.t.) administration of leu-enkephalin or spinorphin inhibited the allodynia induced by intrathecal nociceptin in a dose-dependent manner. Furthermore, spinorphin enhanced the inhibitory effect of enkephalin on allodynia induced by nociceptin. Naloxone antagonized both inhibitory effects of leu-enkephalin and spinorphin, suggesting that the endogenous opioidergic system can modulate allodynia. Intracerebroventricular (i.c.v.) administration of leu-enkephalin increased the nociceptive threshold of heat or mechanical stimulation to a mouse. Although i.c.v. administration of spinorphin had no effect on the threshold of heat or mechanical stimulation, spinorphin enhanced and prolonged the antinociceptive effect of leu-enkephalin. The enhancement of spinorphin on the antinociception produced by leu-enkephalin was reversed by pretreatment with naloxone. From these results, it is suggested that the effects of spinorphin on enkephalin-induced anti-allodynic and antinociceptive effects are due to inhibition of enkephalin-degrading enzymes.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 87 (4), 261-267, 2001

    公益社団法人 日本薬理学会

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