TY - JOUR
T1 - Tachykinin-independent effects of capsaicin on smooth muscle in human isolated bronchi
AU - Ellis, James L.
AU - Sham, James S.K.
AU - Undem, Bradley J.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
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U2 - 10.1164/ajrccm.155.2.9032224
DO - 10.1164/ajrccm.155.2.9032224
M3 - Article
C2 - 9032224
AN - SCOPUS:0031045816
SN - 1073-449X
VL - 155
SP - 751
EP - 755
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 2
ER -