A study on function mechanism of a novel endogenous

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Spinorphin is a novel endogenous pain-regulated substance whic modulated an enkephalin-degrading activity. In this study, we found that spinorphin causes a significant inhibition of inflammatory responses by human PMNs stimulated with FMLP and may be a new endogenous anti-inflammatory peptide which is mediated in part through the suppression in [Ca^<2+>] i changes. Next we examined the effects of spinorphin, using an in vivo system involving mouse air-pouch as a model of acute inflammatory response. In this model carrageenan and PMNs accumulation at inflammatory sites was an indicator of an acute inflammatory response. Intravenous administration of spinorphin within air-pouch site elicited by carrageenan, the inhibition being 64%, compared to the saline-treated group. Combination of leuhistin, an inhibitor of aminopeptidase N,significantly suppressed PNMs accumulation induced carrageenan. In the future, spinorphin will be an important tool for use in clarifying of neuropeptide-induced biological phenomena such as enkephalin mediated pain and inflammation.