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The effect of a tachykinin NK 1 receptor antagonist, SR140333, on oedema formation induced in rat skin by venom from the Phoneutria nigriventer spider
Author(s) -
Palframan R.T.,
Costa S.K.P.,
Wilsoncroft P.,
Antunes E.,
Nucci G.,
Brain S.D.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15402.x
Subject(s) - calcitonin gene related peptide , medicine , endocrinology , tachykinin receptor , agonist , extravasation , antagonist , receptor , receptor antagonist , bradykinin , nk1 receptor antagonist , chemistry , neuropeptide , substance p , pharmacology , biology , immunology
1 The possibility that tachykinin NK 1 receptors are involved in the plasma extravasation evoked by intradermal (i.d.) injection of Phoneutria nigriventer venom (PNV) in rat dorsal skin in vivo has been investigated. 2 Local oedema formation induced by the i.d. injection of test agents was measured by the extravascular accumulation of intravenously (i.v.) injected 125 I‐labelled human serum albumin over a 30 min period. 3 The tachykinin NK 1 agonist, GR73632 (30 pmol per site), induced local oedema formation which was potentiated by co‐injection with the neuropeptide vasodilator, calcitonin gene‐related peptide (CGRP, 10 pmol per site). The non‐peptide tachykinin NK 1 receptor antagonist, SR140333 (0.03‐1 nmol per site co‐injected, i.d.) significantly inhibited (0.3 nmol per site, P <0.05; 1 nmol per site, P <0.001) local oedema formation induced by GR73632 with CGRP but not that induced by histamine (10 nmol per site) with CGRP. 4 PNV (0.03‐0.3 μg per site) injected i.d. induced dose‐dependent local oedema formation. SR140333 (1 nmol per site, co‐injected i.d.) inhibited oedema formation; with complete inhibition observed at doses of 0.03 μg ( P <0.05) and 0.1 μg ( P <0.001); and partial inhibition (50%) observed with the highest dose of PNV, 0.3 μg ( P <0.05). 5 Local oedema formation induced by PNV was not affected by systemic pretreatment with the bradykinin B 2 receptor antagonist, Hoe 140 (80 nmol kg −1 , i.v.), which was used at a dose which significantly inhibited oedema formation by bradykinin (1 nmol per site). 6 Local oedema formation induced by PNV was significantly inhibited ( P <0.01) by co‐injection of the histamine H 1 receptor antagonist, mepyramine (2.5 nmol per site), together with the 5‐hydroxytryptamine (5‐HT) antagonist, methysergide (2.8 nmol per site). 7 In the presence of all three antagonists (mepyramine 2.5 nmol per site; methysergide, 2.8 nmol per site and SR140333 1 nmol per site), the plasma extravasation induced by PNV was further significantly inhibited ( P <0.001, when compared with PNV injected i.d. alone; P <0.05 when compared with PNV co‐injected with mepyramine and methysergide and P <0.01, when compared with PNV co‐injected with SR140333). 8 These results suggest that oedema formation evoked by i.d. PNV in rat skin may be partially mediated via a mechanism involving tachykinin NK 1 receptors and that this effect is independent of histamine and 5‐HT.