Abstract
The 37-amino-acid calcitonin gene-related peptide (CGRP) occurs as a result of alternative processing of mRNA from the calcitonin gene1. The potency of CGRP as a vasodilator2 and the occurrence of the peptide in nerves associated with blood vessels1,3 suggest an important role for CGRP in the regulation of blood flow. The finding that CGRP induces protracted vasodilatation when administered extra-vascularly2,4, to mimic release from nerves, has led us to investigate how the vasodilator activity of CGRP is controlled in vivo. CGRP is often co-localized with substance P in C-fibre nerves5,6. Here, we demonstrate that injection of CGRP with substance P into human skin converts the long-lasting vasodilatation induced by CGRP into a transient response. Experiments in animals reveal that the phenomenon is dependent on the action of proteases from mast cells stimulated by substance P. The results reveal a new regulatory interaction between two neuropeptides and provide evidence for an in vivo role for mast cell proteases.
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Brain, S., Williams, T. Substance P regulates the vasodilator activity of calcitonin gene-related peptide. Nature 335, 73–75 (1988). https://doi.org/10.1038/335073a0
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DOI: https://doi.org/10.1038/335073a0
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