title: Inhibition of neuropeptide degradation suppresses sweating but increases the area of the axon reflex flare.
abstract: 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 (ACh) 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 ACh-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.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schlereth
authors.forename: Markus
authors.initials: M
authors.lastname: Breimhorst
authors.forename: Nicolas
authors.initials: N
authors.lastname: Werner
authors.forename: Katrin
authors.initials: K
authors.lastname: Pottschmidt
authors.forename: Peter D
authors.initials: PD
authors.lastname: Drummond
authors.forename: Frank
authors.initials: F
authors.lastname: Birklein
mesh_terms: D000328:Adult; D001369:Axons / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology; D012018:Reflex / Q000502:physiology; D012867:Skin / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013546:Sweating / Q000187:drug effects / Q000502:physiology*
chemical_list: D006020:Glycopeptides; D011480:Protease Inhibitors; D013373:Substance P; D015260:Neprilysin; D015740:Calcitonin Gene-Related Peptide; C008890:phosphoramidon