Effect of capsaicin on PAF-induced bronchial hyperresponsiveness and pulmonary cell accumulation in the rabbit.
1 Platelet activating factor (PAF), but not the carrier molecule bovine serum albumin (BSA) induced bronchoconstriction in the anaesthetized rabbit. This bronchoconstriction was not altered by prior treatment with capsaicin. 2 Rabbits demonstrated increased airways responsiveness to histamine 24h after exposure to PAF but not to BSA. PAF failed to increase airways responsiveness to histamine in animals pretreated with capsaicin (80 mg kg-1). 3 A significant increase in inflammatory cells was obtained in bronchoalveolar lavage (BAL) 24h after PAF exposure in vehicle-treated rabitts. This was associated with an increase in the numbers of neutrophils and eosinophils. Capsaicin treatment inhibited the PAF-induced influx of inflammatory cells found in BAL, although this was not associated with an inhibition of PAF-induced pulmonary eosinophilia. 4 Capsaicin-induced motor effects were modest in epithelium-intact rabbit bronchial preparations, but were significantly enhanced in epithelium-denuded preparations in the presence of thiorphan. The contractile response to capsaicin was significantly inhibited in tissues exposed to a consecutive dose of capsaicin. Furthermore, ruthenium red abolished capsaicin-induced contraction in epithelium-denuded preparations. 5 Tissue content of calcitonin gene-related peptide-like immunoreactivity and substance P-like immunoreactivity was not reduced in bronchus and iris obtained from capsaicin-treated rabbits, although capsaicin-induced contractile responses in rabbit bronchus obtained from animals previously treated with capsaicin were significantly reduced. Furthermore, airway responses to histamine, methacholine and electrical field stimulation in vitro, were not altered by pretreatment of rabbits in vivo for 3 days with capsaicin. 6. In conclusion, PAF-induced airways responsiveness and pulmonary cell accumulation is inhibited by in vivo capsaicin pretreatment in the rabbit, via a mechanism that may not involve depletion of sensory neuropeptides.
Spina
D
D
Department of Pharmacology, Kings College London.
McKenniff
M G
MG
Coyle
A J
AJ
Seeds
E A
EA
Tramontana
M
M
Perretti
F
F
Manzini
S
S
Page
C P
CP
D000758:Anesthesia; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011817:Rabbits; D011863:Radioimmunoassay; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D010972:Platelet Activating Factor; D012710:Serum Albumin, Bovine; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin