Blockade by theophylline of capsaicin-induced motor effects in guinea-pig airways.
The effect of theophylline was tested on the capsaicin-induced increase in insufflation pressure in anaesthetized guinea-pigs and contraction of isolated tracheal spirals. Theophylline (6.25-25 mg/kg i.v.) inhibited in a marked, prolonged and dose-related manner the increase in insufflation pressure elicited by i.v. injection of capsaicin (2-10 micrograms/kg). Theophylline, even at plasma concentrations as low as 15-23 micrograms/ml (which are within or slightly higher than the therapeutic range in humans) produced an inhibition of about 30-50% of capsaicin-induced bronchospasm. Theophylline was significantly less effective in antagonizing the bronchospasm elicited by maximally effective dose (100 micrograms/kg i.v.) of acetylcholine as well as by a dose equieffective to capsaicin 10 micrograms/kg (i.e. acetylcholine 50 micrograms/kg). Theophylline (30 microM-1 mM) also inhibited potently and concentration dependently the capsaicin-induced contraction in vitro and, again, it was significantly less effective against cholinomimetic-induced responses. These data suggest that theophylline can interfere, at therapeutic doses, with some process(es) selectively involved in capsaicin-induced neuropeptide-mediated bronchoconstriction. Since capsaicin-sensitive sensory fibers are thought to be involved in the pathogenesis of bronchial hyperreactivity and asthma, these inhibitory actions of theophylline might be relevant for its therapeutic effects.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D013806:Theophylline / Q000097:blood / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D002217:Carbachol; D013806:Theophylline; D000109:Acetylcholine; D002211:Capsaicin