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Spinorphin, an endogenous inhibitor of enkephalin-degrading enzymes, potentiates leu-enkephalin-induced anti-allodynic and antinociceptive effects in mice.
Jpn J Pharmacol. 2001 Dec; 87(4):261-7.JJ

Abstract

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.

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Authors+Show Affiliations

Honda M
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Okutsu H
No affiliation info available
Matsuura T
No affiliation info available
Miyagi T
No affiliation info available
Yamamoto Y
No affiliation info available
Hazato T
No affiliation info available
Ono H
No affiliation info available

MeSH

AnalgesicsAnimalsDrug SynergismEnkephalin, LeucineInjections, IntraventricularMaleMiceNaloxoneNeprilysinNociceptorsOligopeptidesOpioid PeptidesPain MeasurementPain ThresholdProtease Inhibitors

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11829145

Citation

Honda, M, et al. "Spinorphin, an Endogenous Inhibitor of Enkephalin-degrading Enzymes, Potentiates Leu-enkephalin-induced Anti-allodynic and Antinociceptive Effects in Mice." Japanese Journal of Pharmacology, vol. 87, no. 4, 2001, pp. 261-7.
Honda M, Okutsu H, Matsuura T, et al. Spinorphin, an endogenous inhibitor of enkephalin-degrading enzymes, potentiates leu-enkephalin-induced anti-allodynic and antinociceptive effects in mice. Jpn J Pharmacol. 2001;87(4):261-7.
Honda, M., Okutsu, H., Matsuura, T., Miyagi, T., Yamamoto, Y., Hazato, T., & Ono, H. (2001). Spinorphin, an endogenous inhibitor of enkephalin-degrading enzymes, potentiates leu-enkephalin-induced anti-allodynic and antinociceptive effects in mice. Japanese Journal of Pharmacology, 87(4), 261-7.
Honda M, et al. Spinorphin, an Endogenous Inhibitor of Enkephalin-degrading Enzymes, Potentiates Leu-enkephalin-induced Anti-allodynic and Antinociceptive Effects in Mice. Jpn J Pharmacol. 2001;87(4):261-7. PubMed PMID: 11829145.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinorphin, an endogenous inhibitor of enkephalin-degrading enzymes, potentiates leu-enkephalin-induced anti-allodynic and antinociceptive effects in mice. AU - Honda,M, AU - Okutsu,H, AU - Matsuura,T, AU - Miyagi,T, AU - Yamamoto,Y, AU - Hazato,T, AU - Ono,H, PY - 2002/2/7/pubmed PY - 2002/7/24/medline PY - 2002/2/7/entrez SP - 261 EP - 7 JF - Japanese journal of pharmacology JO - Jpn J Pharmacol VL - 87 IS - 4 N2 - 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. SN - 0021-5198 UR - https://www.unboundmedicine.com/medline/citation/11829145/Spinorphin_an_endogenous_inhibitor_of_enkephalin_degrading_enzymes_potentiates_leu_enkephalin_induced_anti_allodynic_and_antinociceptive_effects_in_mice_ L2 - https://joi.jlc.jst.go.jp/JST.JSTAGE/jjp/87.261?from=PubMed DB - PRIME DP - Unbound Medicine ER -