Inhibitory action of spinorphin, an endogenous regulator of enkephalin-degrading enzymes, on carrageenan-induced polymorphonuclear neutrophil accumulation in mouse air-pouches.
Whether spinorphin, an endogenous regulator of enkephalin-degrading enzymes, plays a role in an anti-inflammatory action was examined, using a mouse air-pouch assay as a model of acute inflammation. Repeated intravenous administration (6 times) of spinorphin every hour significantly suppressed carrageenan-induced polymorphonuclear neutrophil (PMN) accumulation, an indicator of inflammation (3.21+/-0.95 x 10[6] cells vs 8.92+/-0.96 x 10[6] cells, 10mg/kg spinorphin-treated vs saline-treated group, n=5, P<0.01) at 6 hr. The combination of spinorphin and leuhistin (2 mg/kg, i.v.), a specific inhibitor of aminopeptidase N (APN), markedly suppressed the PMN accumulation induced by carrageenan (1.11+/-0.17 x 10[6] cells, 88% inhibition compared to the saline-treated group, n=5, P<0.01). This inhibition was less than, but comparable to that of dexamethasone (30 mg/kg/one shot, i. v.), a representative anti-inflammatory drug. These results indicate that spinorphin may be an endogenous anti-inflammatory regulator, its inhibitory activity being modulated by APN.
Yamamoto
Y
Y
Department of Cancer Therapeutics, The Tokyo Metropolitan Institute of Medical Science, Japan. yyamamoto@rinshoken.or.jp
Kanazawa
H
H
Shimamura
M
M
Ueki
M
M
Hazato
T
T
D000626:Aminopeptidases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D002449:Cell Aggregation; D005079:Excipients / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000378:metabolism / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D005079:Excipients; D009842:Oligopeptides; D011480:Protease Inhibitors; C082392:spinorphin; D002351:Carrageenan; D000626:Aminopeptidases; C025579:enkephalin degrading enzyme