title: In vivo exposure to nitrogen dioxide (NO2) induces a decrease in calcitonin gene-related peptide (CGRP) and tachykinin immunoreactivity in guinea-pig peripheral airways.
abstract: The mammalian respiratory tract is densely innervated by sensory and autonomic fibres. Subsets of the nerves contain bioactive regulatory peptides, such as substance P, calcitonin gene-related peptide (CGRP), and neurokinins. The sensory nervous system responds to inhaled irritants, resulting in a release of neuropeptides and, thus, a decrease in the peptide immunoreactivity of the fibres. We examined the effects of inhaled nitrogen dioxide (NO2), a well-known indoor and outdoor air pollutant, on pulmonary sensory neuropeptides. Guinea-pigs were exposed for 4 h to 18 parts per million (ppm) NO2 or to air (n = 5 each). At the end of the exposure, they were killed with urethane and their lungs were fixed in 1% paraformaldehyde in phosphate-buffered saline. Cryostat sections were stained with antisera to an anatomical nerve marker, protein gene product (PGP) 9.5, and to CGRP and tachykinins, utilizing the avidin-biotinylated peroxidase method. In the noncartilaginous airways (diameter < 250 microns) of NO2-exposed animals, less tachykinin- and CGRP-immunoreactive nerve fibres were found compared with controls. No change was seen in the total nerve fibre distribution (PGP 9.5). It is concluded that the peptidergic nerves of guinea-pig peripheral airways are a sensitive indicator of exposure to nitrogen dioxide.
authors.affiliation: Institute of Occupational Medicine, University of Padova, Italy.
authors.forename: R E
authors.initials: RE
authors.lastname: Lucchini
authors.forename: D R
authors.initials: DR
authors.lastname: Springall
authors.forename: P
authors.initials: P
authors.lastname: Chitano
authors.forename: L M
authors.initials: LM
authors.lastname: Fabbri
authors.forename: J M
authors.initials: JM
authors.lastname: Polak
authors.forename: C E
authors.initials: CE
authors.lastname: Mapp
mesh_terms: D000280:Administration, Inhalation; D000393:Air Pollutants / Q000494:pharmacology; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000037:antagonists & inhibitors*; D004781:Environmental Exposure; D006168:Guinea Pigs; D007124:Immunoenzyme Techniques; D007509:Irritants / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000294:innervation / Q000473:pathology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000032:analysis; D015288:Neurokinin A / Q000032:analysis / Q000037:antagonists & inhibitors; D015287:Neurokinin B / Q000032:analysis / Q000037:antagonists & inhibitors; D009475:Neurons, Afferent / Q000187:drug effects / Q000648:ultrastructure; D009585:Nitrogen Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D010083:Oxidants, Photochemical / Q000008:administration & dosage / Q000494:pharmacology*; D013373:Substance P / Q000032:analysis / Q000037:antagonists & inhibitors; D015320:Tachykinins / Q000032:analysis / Q000037:antagonists & inhibitors*; D013869:Thiolester Hydrolases / Q000032:analysis; D043222:Ubiquitin Thiolesterase
chemical_list: D000393:Air Pollutants; D007509:Irritants; D009419:Nerve Tissue Proteins; D010083:Oxidants, Photochemical; D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide; D009585:Nitrogen Dioxide