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

Research output: Contribution to journalArticle

Abstract

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 μM and averaged > 40% maximal contraction at 300 μM (the highest concentration studied). The capsaicin-induced contractions were mimicked by resiniferatoxin (0.1-10 μM) and inhibited by the putative capsaicin receptor antagonist, capsazepine (10 μM). The contractile response to capsaicin was not affected by the potent NK-2 selective antagonist SR 48968 (0.3 μM), whereas responses to concentrations of neurokinin A (10 nM), neurokinin B (0.1 μM), substance P (1 μM), neuropeptide γ (10 nM), and neuropeptide K (10 nM) which produced similar- size contractions were almost abolished by 0.1 μM 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 μM). In whole-cell patch- damp 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 μM. 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.

Original languageEnglish (US)
Pages (from-to)751-755
Number of pages5
JournalAmerican journal of respiratory and critical care medicine
Volume155
Issue number2
DOIs
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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