EFFECT OF A NEUROKININ-1 (NK1) RECEPTOR ANTAGONIST ON EDEMA FORMATIONINDUCED BY TACHYKININS, CARRAGEENAN AND AN ALLERGIC RESPONSE IN GUINEA-PIG SKIN

The effect of the neurokinin-1 (NK1) receptor antagonist RP67580 in mo dulating inflammatory oedema formation has been investigated in guinea -pig skin. Oedema formation was measured over 30 min by the extravascu lar accumulation of intravenously-injected I-125-albumin in the anaest hetised guinea-pig. RP67580 was injected intradermally with the agents under test. Intradermal RP67580 (10 nmol/site) inhibits oedema format ion induced by substance P (30 pmol) and neurokinin A (100 pmol), but not that induced by bradykinin (10-1000 pmol) or histamine(10 nmol). S ubstance P-induced oedema formation is similar in control (saline) and mepyramine (histamine H-1 receptor antagonist) pretreated guinea-pigs suggesting a minimal involvement of histamine in substance P induced oedema formation in guinea-pig skin. Oedema formation induced by intra dermal carrageenin (0.2%) was not inhibited by RP67580 (1-10 nmol). A significant but partial inhibition of oedema formation induced in a pa ssive cutaneous anaphylaxis (PCA) response was observed. The oedema fo rmation in the PCA was inhibited 50% by mepyramine pretreatment but in the presence of mepyramine no further inhibition of the PCA response by RP67580 was observed.