Airways are densely innervated by
capsaicin-sensitive sensory neurons expressing transient receptor potential vanilloid 1 (TRPV1) receptors/
ion channels, which play an important regulatory role in inflammatory processes via the release of sensory
neuropeptides. The aim of the present study was to investigate the role of TRPV1 receptors in
endotoxin-induced airway
inflammation and consequent
bronchial hyperreactivity with functional, morphological, and biochemical techniques using receptor gene-deficient mice.
Inflammation was evoked by
intranasal administration of Escherichia coli
lipopolysaccharide (60 microl, 167 microg/ml) in TRPV1 knockout (TRPV1(-/-)) mice and their wild-type counterparts (TRPV1(+/+)) 24 h before measurement. Airway reactivity was assessed by unrestrained whole body plethysmography, and its quantitative
indicator, enhanced pause (Penh), was calculated after inhalation of the bronchoconstrictor
carbachol. Histological examination and spectrophotometric
myeloperoxidase measurement was performed from the lung.
Somatostatin concentration was measured in the lung and plasma with radioimmunoassay.
Bronchial hyperreactivity, histological lesions (perivascular/peribronchial
edema, neutrophil/macrophage infiltration, goblet cell
hyperplasia), and
myeloperoxidase activity were significantly greater in TRPV(-/-) mice.
Inflammation markedly elevated lung and plasma
somatostatin concentrations in TRPV1(+/+) but not TRPV1(-/-) animals. In TRPV1(-/-) mice, exogenous administration of
somatostatin-14 (4 x 100 microg/kg ip) diminished
inflammation and hyperreactivity. Furthermore, in wild-type mice, antagonizing
somatostatin receptors by cyclo-
somatostatin (4 x 250 microg/kg ip) increased these parameters. This study provides the first evidence for a novel counterregulatory mechanism during
endotoxin-induced airway
inflammation, which is mediated by
somatostatin released from sensory nerve terminals in response to activation of TRPV1 receptors of the lung. It reaches the systemic circulation and inhibits
inflammation and consequent
bronchial hyperreactivity.