Interactions between tachykinins and CGRP in human skin

Substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) coexist in nerve fibres in the skin. CGRP causes erythema upon intracutaneous injection. The erythema is independent of axon reflexes and release of mast cell histamine. SP is known to produce a flare reaction that is dependent on axon reflexes and release of mast cell histamine. The flare reaction to NKA is known to depend predominantly on axon reflexes. The purpose of the present study was to investigate possible cooperation between SP and CGRP. SP was found to shorten the duration of the reddening induced by CGRP, injected concomitantly. NKA did not shorten the duration of the CGRP response. Local elimination of mast cells in the skin by treatment with compound 48/80 had the effect that SP lost its ability to shorten CGRP-evoked erythema. These observations support the suggestion that an SP-evoked release of proteolytic enzymes from mast cells could lead to accelerated degradation of CGRP