Different ion channel control pH6-induced bronchoconstriction and calcitonin gene-related peptide release in the guinea-pig lung.
We have studied the bronchoconstriction and the release of calcitonin gene-related peptide-like immunoreactivity induced by perfusion of pH6 buffer in the isolated guinea-pig perfused lung. Both bronchoconstriction and peptide release were completely abolished after systemic capsaicin pretreatment. Ca(2+)-free pH6 buffer infusion also completely inhibited the bronchial response, whereas the calcitonin gene-related peptide-like immunoreactivity overflow was significantly reduced. omega-Conotoxine and omega-agatoxin IVA known as N-, L- and P-type Ca2+ channel blocker, respectively, and the Na+ channel blocker tetrodotoxin decreased significantly the pH6-induced bronchial response and calcitonin gene-related peptide like immunoreactivity overflow. Nifedipine was without influence suggesting the involvement of both P- and N-type Ca2+ channel as well as the activation of an axon reflex. Ruthenium red had a more pronounced reduction effect on the functional response than on the peptide release. Ryanodine and caffeine are both agents known to influence Ca2+ release from sarcoplasmic reticulum. Ryanodine significantly reduced both bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow. Caffeine as well as theophylline and the Na(+)-H+ blocker, dimethylamiloride, largely depressed the functional response while producing a significant increase of calcitonin gene-related peptide-like immuno-reactivity basal value. The pH6-induced peptide overflow was slightly inhibited after caffeine and dimethylamiloride pre-treatment whereas no significant change was observed after theophylline. It is concluded that multiple ion channels including different type of Ca2+ channels appear to participate in pH6-induced bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity release in the guinea-pig lung.
Auberson
S
S
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden. serge.auberson@hcuge.ch
Lacroix
J S
JS
Lundberg
J M
JM
D000818:Animals; D016084:Bronchoconstriction; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000502:physiology*; D008168:Lung / Q000378:metabolism*; D008297:Male; D012430:Ruthenium Red / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D007473:Ion Channels; D012430:Ruthenium Red; D012433:Ryanodine; D013806:Theophylline; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D002118:Calcium