Effect of a neurokinin-1 (NK1) receptor antagonist on oedema formation induced by tachykinins, carrageenin and an allergic response in guinea-pig skin.
The effect of the neurokinin-1 (NK1) receptor antagonist RP67580 in modulating inflammatory oedema formation has been investigated in guinea-pig skin. Oedema formation was measured over 30 min by the extravascular accumulation of intravenously-injected 125I-albumin in the anaesthetised guinea-pig. RP67580 was injected intradermally with the agents under test. Intradermal RP67580 (10 nmol/site) inhibits oedema formation induced by substance P (30 pmol) and neurokinin A (100 pmol), but not that induced by bradykinin (10-1000 pmol) or histamine (10 nmol). Substance P-induced oedema formation is similar in control (saline) and mepyramine (histamine H1 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 intradermal carrageenin (0.2%) was not inhibited by RP67580 (1-10 nmol). A significant but partial inhibition of oedema formation induced in a passive cutaneous anaphylaxis (PCA) response was observed. The oedema formation 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.
Wilsoncroft
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Division of Biomedical Sciences, King's College, London, UK.
Euzger
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Brain
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D000818:Animals; D001920:Bradykinin; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology*; D006168:Guinea Pigs; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control*; D007271:Injections, Intradermal; D054833:Isoindoles; D008297:Male; D015288:Neurokinin A; D064729:Neurokinin-1 Receptor Antagonists; D011738:Pyrilamine / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000276:immunology*; D013373:Substance P / Q000037:antagonists & inhibitors; D015320:Tachykinins
D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D015320:Tachykinins; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D015288:Neurokinin A; D002351:Carrageenan; D011738:Pyrilamine; D015740:Calcitonin Gene-Related Peptide; D001920:Bradykinin