P. Wilsoncroft et al., EFFECT OF A NEUROKININ-1 (NK1) RECEPTOR ANTAGONIST ON EDEMA FORMATIONINDUCED BY TACHYKININS, CARRAGEENAN AND AN ALLERGIC RESPONSE IN GUINEA-PIG SKIN, Neuropeptides, 26(6), 1994, pp. 405-411
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.