Evidence that calcitonin gene-related peptide contributes to inflammation in the skin and joint.
Calcitonin gene-related peptide produces dose-related vasodilatation after intradermal injection in several species. In the present study, CGRP increased blood flow in rabbit skin but had no direct effect on edema formation in rat or rabbit skin or in the rat knee joint. However, CGRP produced significant potentiation of edema formation when co-injected with histamine, a potent mediator of increased vascular permeability. Therefore, release of CGRP from stimulated C-fiber nerves may contribute to the vascular changes that are an integral part of the inflammatory process. The activity of the putative CGRP antagonist CGRP8-37 (300 pmol) against CGRP was also investigated in rabbit and rat skin. Whereas it was found to selectively antagonize the effects of CGRP in rabbit skin, the antagonist produced edema in rat skin at the same dose. Thus, CGRP8-37 may be used in the rabbit to study the effects of endogenously released CGRP, but caution is required when this antagonist is used in the rat.
Brain
S D
SD
Biomedical Sciences Division, King's College, London, United Kingdom.
Cambridge
H
H
Hughes
S R
SR
Wilsoncroft
P
P
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000633:toxicity*; D004487:Edema; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D007457:Iodine Radioisotopes; D007592:Joint Diseases / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism; D012867:Skin / Q000098:blood supply*; D012871:Skin Diseases / Q000139:chemically induced* / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects; D014980:Xenon Radioisotopes
D007457:Iodine Radioisotopes; D012709:Serum Albumin; D014980:Xenon Radioisotopes; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide