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Inhibition of neuropeptide degradation suppresses sweating but increases the area of the axon reflex flare
Author(s) -
Schlereth Tanja,
Breimhorst Markus,
Werner Nicolas,
Pottschmidt Katrin,
Drummond Peter D.,
Birklein Frank
Publication year - 2013
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12122
Subject(s) - phosphoramidon , calcitonin gene related peptide , chemistry , microdialysis , endocrinology , medicine , substance p , neuropeptide , cholinergic , acetylcholine , calcitonin , pharmacology , neprilysin , biochemistry , extracellular , enzyme , receptor
The neuropeptides CGRP (calcitonin gene‐elated peptide) and substance P ( SP ) mediate neurogenic inflammation. Both are degraded by the neutral endopeptidase ( NEP ) which can be blocked by phosphoramidon. The aim was to evaluate the effect of NEP inhibition on sweating and vasodilatation. Dermal microdialysis was performed on the skin of 39 subjects. Two fibres were perfused with phosphoramidon (0.01%, 0.02% or 0.2%), two with saline. Acetylcholine ( AC h) was either added to the microdialysis perfusate ( n = 30, 10 −2 m ) or thermoregulatory sweating was induced ( n = 9). Co‐application of phosphoramidon reduced cholinergic and thermoregulatory sweating. However, the flare size – a localized increase in superficial blood flow after AC h‐application – was significantly increased. The increase in flare size is most probably due to increased CGRP levels. The inhibition of sweating by phosphoramidon may involve an increase in SP , a reduction in CGRP ‐degradation fragments or a direct inhibitory action of phosphoramidon.