Airway hyper-responsiveness to neurokinin A and bradykinin following Mycoplasma pneumoniae infection associated with reduced epithelial neutral endopeptidase.
To determine whether mycoplasma infection produces airway hyper-responsiveness to tachykinins and bradykinin and, if so, to elucidate the role of neutral endopeptidase (NEP), isolated hamster tracheal segments were studied under isometric conditions in vitro. Nasal inoculation with Mycoplasma pneumoniae potentiated contractile responses to neurokinin A and bradykinin, causing a leftward shift of the dose-response curves to a lower concentration by 1 log unit for each agonist, whereas there was no response with acetylcholine. Pretreatment of tissues with the NEP inhibitor phosphoramidon augmented neurokinin A- and bradykinin-induced contractions in saline-treated control tissues, but did not further potentiate the responsiveness in M. pneumoniae-infected tissues. NEP activity in the tracheal epithelium, but not in epithelium-denuded tissues, was decreased in infected animals. These results suggest that M. pneumoniae infection causes airway bronchoconstrictor hyper-responsiveness to neurokinin A and bradykinin and that this effect may be associated with an inhibition of epithelial NEP activity.
Tamaoki
Jun
J
First Department of Medicine8-1 Kawada-Cho, Shinjuku, Tokyo 162Japan.
Chiyotani
Atsushi
A
First Department of Medicine8-1 Kawada-Cho, Shinjuku, Tokyo 162Japan.
Tagaya
Etsuko
E
First Department of Medicine8-1 Kawada-Cho, Shinjuku, Tokyo 162Japan.
Araake
Minako
M
Department of Microbiology, Tokyo Women's Medical College8-1 Kawada-Cho, Shinjuku, Tokyo 162Japan.
Nagai
Atsushi
A
First Department of Medicine8-1 Kawada-Cho, Shinjuku, Tokyo 162Japan.
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001920:Bradykinin / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology; D006224:Cricetinae; D004848:Epithelium / Q000201:enzymology; D006020:Glycopeptides / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D009177:Mycoplasma pneumoniae / Q000276:immunology; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015288:Neurokinin A / Q000494:pharmacology*; D011019:Pneumonia, Mycoplasma / Q000276:immunology / Q000503:physiopathology*; D011480:Protease Inhibitors / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000503:physiopathology*
D000907:Antibodies, Bacterial; D006020:Glycopeptides; D011480:Protease Inhibitors; D015288:Neurokinin A; D015260:Neprilysin; D001920:Bradykinin; C008890:phosphoramidon