Sensory neuropeptide-mediated bronchoconstriction of the guinea pig lung by diamide; a comparison to hydrogen peroxide.
The effect of the thiol oxidizing agent diamide on airway conductance, dynamic compliance and perfusion flow of isolated perfused and ventilated guinea pig lungs was investigated. When infused in the pulmonary circulation, diamide (100 microM) induced bronchoconstriction, but no effect on perfusion flow was observed. Although diamide exposure induced the formation of thromboxane A2, the thromboxane/prostaglandin endoperoxide receptor antagonist L-670,596 did not affect the decrease in conductance and compliance induced by diamide. Diamide induced the release of the sensory neuropeptide calcitonin gene-related peptide. The bronchoconstriction and the release of calcitonin gene-related peptide induced by diamide were abolished by capsaicin pretreatment of the guinea pigs. Combined pretreatment with the NK1 and NK2 receptor antagonists, CP-96,345 and SR-48968, attenuated the effect of diamide. Hydrogen peroxide-induced vaso- and bronchoconstriction was not affected by capsaicin-pretreatment, nor did hydrogen peroxide induce detectable release of calcitonin gene-related peptide. The results indicate that diamide activates sensory nerves and induces neuropeptide release and neurokinin receptor-mediated bronchoconstriction in the isolated perfused and ventilated guinea pig lung.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
G
G
Bannenberg
M
M
Kimland
A
A
Ryrfeldt
J M
JM
Lundberg
P
P
Moldéus
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D003958:Diamide / Q000494:pharmacology*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects*; D008297:Male; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D013931:Thromboxanes / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D001549:Benzamides; D001713:Biphenyl Compounds; D002227:Carbazoles; D009479:Neuropeptides; D010880:Piperidines; D013931:Thromboxanes; D003958:Diamide; C061299:L 670596; C073839:SR 48968; D015288:Neurokinin A; D006861:Hydrogen Peroxide; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; C066892:CP 96345