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Interactions between the tachykinins and calcitonin gene‐related peptide lead to the modulation of oedema formation and blood flow in rat skin
Author(s) -
Brain S.D.,
Williams T.J.
Publication year - 1989
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.1476-5381.1989.tb11926.x
Subject(s) - calcitonin gene related peptide , substance p , neurokinin a , neurokinin b , endocrinology , medicine , neuropeptide , antagonist , histamine , vasodilation , chemistry , calcitonin , tachykinin receptor 1 , nk1 receptor antagonist , neurogenic inflammation , pharmacology , receptor
1 The mechanisms involved in tachykinin‐induced oedema were investigated in rat skin and interactions between the tachykinins and calcitonin gene‐related peptide (CGRP) were studied. 2 Intradermal injections of the tachykinins, substance P, neurokinin A and neurokinin B, stimulated local oedema formation which was in each case potentiated by co‐injection of the vasodilator CGRP. Oedema induced by substance P, in the presence and absence of CGRP, was significantly inhibited by pretreatment of rats with a combination of the histamine H 1 antagonist, mepyramine, and the 5‐hydroxytryptamine antagonist, methysergide. Oedema induced by neurokinin A or B was not inhibited by this pretreatment. 3 Intradermally‐injected CGRP induced a long lasting increase in local blood flow, which was measured with a laser Doppler blood flow meter. The simultaneous injection of substance P, but not of the structurally‐related neurokinins, caused a loss of the prolonged vasodilator activity of CGRP. 4 These results show that oedema induced by substance P is partially dependent on mast cell amines and that only substance P causes a loss of the prolonged vasodilator activity of CGRP. 5 We suggest that the ability of substance P to prevent the persistent vasodilator activity of CGRP may be a direct consequence of substance P‐induced activation of mast cells.