The calcitonin gene-related peptide (CGRP) antagonist CGRP(8-37) blocks vasodilatation in inflamed rat skin: involvement of adrenomedullin in addition to CGRP.
The neuropeptide calcitonin gene-related peptide (CGRP) is a potent microvascular vasodilator in rat skin and effects are antagonised by CGRP(8-37). In this study, CGRP(8-37) 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-1beta (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 CGRP(8-37). We show that ADM mRNA expression is increased in rat skin after treatment with IL-1beta and that the IL-1beta-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-1beta-induced vasoactive effects.
Chu
D Q
DQ
Centre for Cardiovascular Biology & Medicine, New Hunt's House, King's College, Guy's Campus, London SE1 1UL, UK.
Legon
S
S
Smith
D M
DM
Costa
S K
SK
Cuttitta
F
F
Brain
S D
SD
D053607:Adrenomedullin; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D003872:Dermatitis / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D008916:Miotics / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply; D014664:Vasodilation / Q000187:drug effects*
D007375:Interleukin-1; D008916:Miotics; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide