Tachykinin-independent effects of capsaicin on smooth muscle in human isolated bronchi

• Published in: American journal of respiratory and critical care medicine Vol. 155; no. 2; p. 751
• Main Authors: Ellis, J L, Sham, J S, Undem, B J
• Format: Journal Article
• Language: English
• Published: United States 01-02-1997
• Subjects: Adult; Benzamides - pharmacology; Bronchi - drug effects; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Cells, Cultured; Diterpenes - pharmacology; Drug Interactions; Female; Humans; Male; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Patch-Clamp Techniques; Piperidines - pharmacology; Tachykinins - adverse effects; Tachykinins - antagonists & inhibitors
• ISSN: 1073-449X
• DOI: 10.1164/ajrccm.155.2.9032224

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.