Involvement of sensory nerves and TRPV1 receptors in the rat airway inflammatory response to two environment pollutants: diesel exhaust particles (DEP) and 1,2-naphthoquinone (1,2-NQ).
The environmental chemical 1,2-naphthoquinone (1,2-NQ) is implicated in the exacerbation of airways diseases induced by exposure to diesel exhaust particles (DEP), which involves a neurogenic-mediated mechanism. Plasma extravasation in trachea, main bronchus and lung was measured as the local (125)I-bovine albumin accumulation. RT-PCR quantification of TRPV1 and tachykinin (NK(1) and NK(2)) receptor gene expression were investigated in main bronchus. Intratracheal injection of DEP (1 and 5 mg/kg) or 1,2-NQ (35 and 100 nmol/kg) caused oedema in trachea and bronchus. 1,2-NQ markedly increased the DEP-induced responses in the rat airways in an additive rather than synergistic manner. This effect that was significantly reduced by L-732,138, an NK(1) receptor antagonist, and in a lesser extent by SR48968, an NK(2) antagonist. Neonatal capsaicin treatment also markedly reduced DEP and 1,2-NQ-induced oedema. Exposure to pollutants increased the TRPV1, NK(1) and NK(2) receptors gene expression in bronchus, an effect was partially suppressed by capsaicin treatment. In conclusion, our results are consistent with the hypothesis that DEP-induced airways oedema is highly influenced by increased ambient levels of 1,2-NQ and takes place by neurogenic mechanisms involving up-regulation of TRPV1 and tachykinin receptors.
Costa
Soraia K P
SK
Department of Pharmacology, Institute of Biosciences (ICB-I), University of São Paulo (USP), São Paulo, SP 05508-900, Brazil. tmausp@yahoo.com
Teles
Aila Mirtes
AM
Kumagai
Yoshito
Y
Brain
Susan D
SD
Teixeira
Simone A
SA
Varriano
Ana A
AA
Barreto
Maria Alice A G
MA
de Lima
Wothan Tavares
WT
Antunes
Edson
E
Muscará
Marcelo N
MN
Costa
Soraia K P
SK
D000393:Air Pollutants / Q000633:toxicity; D000818:Animals; D005260:Female; D007249:Inflammation / Q000378:metabolism; D008297:Male; D009285:Naphthoquinones / Q000633:toxicity*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012137:Respiratory System / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*; D001335:Vehicle Emissions / Q000633:toxicity*
D000393:Air Pollutants; D009285:Naphthoquinones; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D001335:Vehicle Emissions; C040756:1,2-naphthoquinone