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The calcitonin gene-related peptide (CGRP) antagonist CGRP(8-37) blocks vasodilatation in inflamed rat skin: involvement of adrenomedullin in addition to CGRP |
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| Authors: | Chu D Q Legon S Smith D M Costa S K Cuttitta F Brain S D |
| Affiliation: | a Centre for Cardiovascular Biology & Medicine, New Hunt's House, King's College, Guy's Campus, London SE1 1UL, UK b Department of Metabolic Medicine, Imperial College School of Medicine, Hammersmith Campus, DuCane Road, London W12 ONN, UK c Cell and Cancer Biology Branch, Centre for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA |
| Abstract: | The neuropeptide calcitonin gene-related peptide (CGRP) is a potent microvascular vasodilator in rat skin and effects are antagonised by CGRP8–37. In this study, CGRP8–37 significantly (P<0.05) inhibited the time-dependent (3–5 h) increase in skin blood flow measured in the anaesthetised rat, after intradermal administration of the inflammatory cytokine interleukin-1β (3 pmol/site), indicating the involvement of CGRP1 receptors. The CGRP-related peptide adrenomedullin (ADM) is also a potent vasodilator in rat skin, with effects antagonised by CGRP8–37. We show that ADM mRNA expression is increased in rat skin after treatment with IL-1β and that the IL-1β-induced blood flow is blocked by a selective ADM antibody (P<0.05). Thus ADM is expressed locally in the inflamed cutaneous microvasculature where it can, in addition to, or as an alternative to CGRP, contribute to IL-1β-induced vasoactive effects. |
| Keywords: | Adrenomedullin Calcitonin gene-related peptide Interleukin-1β Skin Microvasculature Vasodilator |
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