Different ion channel mechanisms between low concentrations of capsaicin and high concentrations of capsaicin and nicotine regarding peptide release from pulmonary afferents.

Vagal nerve stimulation (1 Hz for 1 min), capsaicin (10(-8) M and 10(-6) M), resiniferatoxin (3 x 10(-10) M) and nicotine (10(-4) M) evoked a non-cholinergic bronchoconstriction in the isolated perfused guinea-pig lung preparation. Simultaneously there was an increase in the perfusate levels of calcitonin gene-related peptide-like immunoreactivity, suggesting release from sensory nerves. Both the bronchoconstriction and peptide release evoked by a low concentration of capsaicin (10(-8) M) and that evoked by nerve stimulation were depressed by tetrodotoxin, suggesting involvement of Na+ channel dependent depolarization. Since the effects of capsaicin (10(-8) M) and vagal nerve stimulation were inhibited by omega-conotoxin but not influenced by nifedipine, the Ca(2+)-channel dependent is probably of N-type. Furthermore, the capsaicin analogue resiniferatoxin also evoked omega-conotoxin sensitive peptide release and bronchoconstriction. At the higher capsaicin concentration (10(-6) M), the functional response was only slightly inhibited by omega-conotoxin or tetrodotoxin indicating that capsaicin at this concentration evoked peptide release and functional effects through other mechanisms, probably involving Ca2+ fluxes in the non-selective cation channel associated with the proposed capsaicin receptor. The nicotine (10(-4) M) evoked peptide release and bronchoconstriction were only marginally influenced by omega-conotoxin or tetrodotoxin. It is concluded that the ion-channel mechanisms underlying the peptide releasing properties of antidromic nerve stimulation and low concentrations of capsaicin are similar and depend on action potential propagation, whereas capsaicin in high, toxic concentration and nicotine mainly act via receptor operated channels.