Selectivity of ruthenium red in inhibiting bronchoconstriction and CGRP release induced by afferent C-fibre activation in the guinea-pig lung.
In the present study we evaluated the effects of ruthenium red, a blocker of transmembrane Ca2+ fluxes, on bronchoconstriction and the release of calcitonin gene-related peptide-like immunoreactivity induced by different stimuli in the isolated perfused guinea-pig lung. Vagal stimulation (1 Hz, 1 min), capsaicin (10(-8) M, 10(-6) M), resiniferatoxin (3 x 10(-10) M), nicotine (10(-4) M), bradykinin (5 x 10(-6) M) and histamine (10(-5) M) evoked bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow. Ruthenium red (5 x 10(-6) M) almost completely inhibited the bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow induced by capsaicin and resiniferatoxin but did not influence the effects induced by vagal nerve stimulation, nicotine, bradykinin or histamine. The 20-deacetylated derivative of resiniferatoxin (ROPA), which lacks the homovanillyl ester group, did not evoke release or bronchoconstriction. Ruthenium red (3 x 10(-4) M) aerosol attenuated the cough induced by nebulized citric acid in conscious guinea-pigs. Citric acid-induced coughing is mediated via capsaicin-sensitive neurons. However, cigarette smoke-induced coughing, which involves capsaicin-resistant mechanisms, was not affected by ruthenium red. In conclusion, ruthenium red selectively inhibits the capsaicin, resiniferatoxin and citric acid-induced excitation of the sensory nerves as revealed by calcitonin gene-related peptide-like immunoreactivity release, bronchoconstriction and coughing, suggesting that these agents share a common mechanism of action.
Lou
Y P
YP
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Karlsson
J A
JA
Franco-Cereceda
A
A
Lundberg
J M
JM
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D003371:Cough / Q000503:physiopathology; D004224:Diterpenes / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008168:Lung / Q000294:innervation / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology*; D012907:Smoking / Q000503:physiopathology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D002951:Citrates; D004224:Diterpenes; D012430:Ruthenium Red; D019343:Citric Acid; D009538:Nicotine; D006632:Histamine; C024353:resiniferatoxin; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin