Article

Role of capsaicin-sensitive afferents and sensory neuropeptides in endotoxin-induced airway inflammation and consequent bronchial hyperreactivity in the mouse.

Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, H-7624 Pécs, Szigeti u. 12., Hungary.
Regulatory Peptides (impact factor: 2.11). 07/2007; 141(1-3):44-54. DOI:10.1016/j.regpep.2006.12.018 pp.44-54
Source: PubMed

ABSTRACT Substance P (SP) and calcitonin gene-related peptide (CGRP) released from capsaicin-sensitive afferents induce neurogenic inflammation via NK(1), NK(2) and CGRP1 receptor activation. This study examines the role of capsaicin-sensitive fibres and sensory neuropeptides in endotoxin-induced airway inflammation and consequent bronchial hyperreactivity with functional, morphological and biochemical techniques in mice. Carbachol-induced bronchoconstriction was measured with whole body plethysmography 24 h after intranasal lipopolysaccharide administration. SP and CGRP were determined with radioimmunoassay, myeloperoxidase activity with spectrophotometry, interleukin-1beta with ELISA and histopathological changes with semiquantitative scoring from lung samples. Treatments with resiniferatoxin for selective destruction of capsaicin-sensitive afferents, NK(1) antagonist SR 140333, NK(2) antagonist SR 48968, their combination, or CGRP1 receptor antagonist CGRP(8-37) were performed. Lipopolysaccharide significantly increased lung SP and CGRP concentrations, which was prevented by resiniferatoxin pretreatment. Resiniferatoxin-desensitization markedly enhanced inflammation, but decreased bronchoconstriction. CGRP(8-37) or combination of SR 140333 and SR 48968 diminished neutrophil accumulation, MPO levels and IL-1beta production, airway hyperresponsiveness was inhibited only by SR 48968. This is the first evidence that capsaicin-sensitive afferents exert a protective role in endotoxin-induced airway inflammation, but contribute to increased bronchoconstriction. Activation of CGRP1 receptors or NK(1)+NK(2) receptors participate in granulocyte accumulation, but NK(2) receptors play predominant role in enhanced airway resistance.

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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

airway hyperresponsiveness
 
airway resistance
 
biochemical techniques
 
calcitonin gene-related peptide
 
capsaicin-sensitive afferents
 
capsaicin-sensitive afferents induce neurogenic inflammation
 
capsaicin-sensitive fibres
 
CGRP1 receptor activation
 
CGRP1 receptor antagonist CGRP(8-37)
 
consequent bronchial hyperreactivity
 
endotoxin-induced airway inflammation
 
first evidence
 
granulocyte accumulation
 
intranasal lipopolysaccharide administration
 
lung samples
 
lung SP
 
MPO levels
 
myeloperoxidase activity
 
neutrophil accumulation
 
study examines