Tachykinin-independent effects of capsaicin on smooth muscle in human isolated bronchi.
Contractile and relaxant responses to capsaicin and resiniferatoxin were examined in human isolated bronchus (5-12 mm o.d.). Bronchi isolated from 10 of 16 lungs contracted in response to capsaicin. The contractions averaged 20% of maximal contraction at 1 microM and averaged > 40% maximal contraction at 300 microM (the highest concentration studied). The capsaicin-induced contractions were mimicked by resiniferatoxin (0.1-10 microM) and inhibited by the putative capsaicin receptor antagonist, capsazepine (10 microM). The contractile response to capsaicin was not affected by the potent NK-2 selective antagonist SR 48968 (0.3 microM), whereas responses to concentrations of neurokinin A (10 nM), neurokinin B (0.1 microM), substance P (1 microM), neuropeptide gamma (10 nM), and neuropeptide K (10 nM) which produced similar-size contractions were almost abolished by 0.1 microM SR 48968. The bronchi isolated from 8 of 16 lungs also exhibited relaxations in response to capsaicin. Capsaicin-induced relaxations were not inhibited by the nitric oxide synthase inhibitor L-nitro-n-arginine (10 microM). In whole-cell patch-clamp experiments on human cultured airway smooth muscle cells, capsaicin was found to enhance outward currents due to the activation of charybdotoxin-sensitive large conductance Ca2+-activated K+ channels. Neither the capsaicin-induced contractions nor the relaxations were mimicked by angiotensin II, bombesin, or calcitonin gene-related peptide at concentrations up to 1 microM. These results suggest that capsaicin and resiniferatoxin can alter smooth muscle tone, but this response does not appear to involve substance P or related neurokinins. Relaxations to capsaicin may, however, involve the activation of large conductance Ca2+-activated K+ channels.
Ellis
J L
JL
Division of Clinical Immunology, The Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224-6801, USA.
Sham
J S
JS
Undem
B J
BJ
D000328:Adult; D001549:Benzamides / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D015320:Tachykinins / Q000009:adverse effects / Q000037:antagonists & inhibitors*
D001549:Benzamides; D004224:Diterpenes; D010880:Piperidines; D015320:Tachykinins; C073839:SR 48968; C024353:resiniferatoxin; C071423:capsazepine; D002211:Capsaicin