Interactions between the tachykinins and calcitonin gene‐related peptide lead to the modulation of oedema formation and blood flow in rat skin

British Journal of Pharmacology - Tập 97 Số 1 - Trang 77-82 - 1989
Susan D. Brain1, T J Williams
1Section of Vascular Biology, MRC Clinical Research Centre, Middlesex.

Tóm tắt

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. 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 H1 antagonist, mepyramine, and the 5‐hydroxytryptamine antagonist, methysergide. Oedema induced by neurokinin A or B was not inhibited by this pretreatment. 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. 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. 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.

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