6533b829fe1ef96bd128a4fd

RESEARCH PRODUCT

Inhibition of neuropeptide degradation suppresses sweating but increases the area of the axon reflex flare.

Katrin PottschmidtNicolas WernerPeter D. DrummondMarkus BreimhorstFrank BirkleinFrank BirkleinTanja Schlereth

subject

AdultMaleMicrodialysismedicine.medical_specialtyCalcitonin Gene-Related PeptideNeuropeptideSubstance PSweatingDermatologyCalcitonin gene-related peptideSubstance PBiochemistrychemistry.chemical_compoundInternal medicineReflexmedicineHumansProtease InhibitorsMolecular BiologySkinNeurogenic inflammationintegumentary systemChemistryPhosphoramidonGlycopeptidesrespiratory systemAxonsEndocrinologyCholinergicFemaleNeprilysinAcetylcholinemedicine.drugBody Temperature Regulation

description

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.

10.1111/exd.12122https://pubmed.ncbi.nlm.nih.gov/23528219