PMID- 11829145
OWN - NLM
STAT- MEDLINE
DCOM- 20020723
LR  - 20190725
IS  - 0021-5198 (Print)
IS  - 0021-5198 (Linking)
VI  - 87
IP  - 4
DP  - 2001 Dec
TI  - Spinorphin, an endogenous inhibitor of enkephalin-degrading enzymes, potentiates 
      leu-enkephalin-induced anti-allodynic and antinociceptive effects in mice.
PG  - 261-7
AB  - 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.
FAU - Honda, M
AU  - Honda M
AD  - Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Science 
      University of Tokyo, Japan.
FAU - Okutsu, H
AU  - Okutsu H
FAU - Matsuura, T
AU  - Matsuura T
FAU - Miyagi, T
AU  - Miyagi T
FAU - Yamamoto, Y
AU  - Yamamoto Y
FAU - Hazato, T
AU  - Hazato T
FAU - Ono, H
AU  - Ono H
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Jpn J Pharmacol
JT  - Japanese journal of pharmacology
JID - 2983305R
RN  - 0 (Analgesics)
RN  - 0 (Oligopeptides)
RN  - 0 (Opioid Peptides)
RN  - 0 (Protease Inhibitors)
RN  - 137201-62-8 (spinorphin)
RN  - 36B82AMQ7N (Naloxone)
RN  - 58822-25-6 (Enkephalin, Leucine)
RN  - EC 3.4.24.11 (Neprilysin)
SB  - IM
MH  - Analgesics/*pharmacology
MH  - Animals
MH  - Drug Synergism
MH  - Enkephalin, Leucine/*pharmacology
MH  - Injections, Intraventricular
MH  - Male
MH  - Mice
MH  - Naloxone/pharmacology
MH  - Neprilysin/*antagonists & inhibitors
MH  - Nociceptors/drug effects
MH  - Oligopeptides/adverse effects/*pharmacology
MH  - Opioid Peptides/adverse effects/*pharmacology
MH  - Pain Measurement/drug effects
MH  - Pain Threshold/drug effects
MH  - Protease Inhibitors/adverse effects/*pharmacology
EDAT- 2002/02/07 10:00
MHDA- 2002/07/24 10:01
CRDT- 2002/02/07 10:00
PHST- 2002/02/07 10:00 [pubmed]
PHST- 2002/07/24 10:01 [medline]
PHST- 2002/02/07 10:00 [entrez]
AID - 10.1254/jjp.87.261 [doi]
PST - ppublish
SO  - Jpn J Pharmacol. 2001 Dec;87(4):261-7. doi: 10.1254/jjp.87.261.