Spinorphin, an Endogenous Inhibitor of Enkephalin-Degrading Enzymes, Potentiates Leu-Enkephalin-Induced Anti-allodynic and Antinociceptive Effects in Mice

The Japanese Journal of Pharmacology

Tomohiro Miyagi²  Hideki Ono²  Tomoyuki Matsuura²  Motoko Honda²  Yukio Yamamoto¹  Tadahiro Hazato¹  Hiroko Okutsu² 

[1] Department of Molecular Oncology, The Tokyo Metropolitan Institute of Medical Science;Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo

关键词: Spinorphin;    Enkephalin-degrading enzyme;    Antinociception;    Allodynia;   

DOI  :  10.1254/jjp.87.261

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(29)Cited-By(11)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.

【 授权许可】

Unknown