A STUDY ON ANTI-INFLAMMATORY ACTION OF A NEW ENDOGENOUS OPIOIDE-REGULATED SUBSTANCE

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Spinorphin is an endogenous pain-regulated substance which 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 in inflammatory sites were used as a inflammation-tiggerring agent 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, and inhibitor of aminopeptidase N,sinergestically suppressed PMNs 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.