Effects of omega-conotoxin GVIA on the activation of capsaicin-sensitive afferent sensory nerves in guinea pig airway tissues.

We examined the effects of Ca2+ channel antagonists on various respiratory reactions induced by the activation of capsaicin-sensitive afferent sensory nerves. Intravenous (i.v.) injection of the N-type Ca2+ channel antagonist omega-conotoxin GVIA (CgTX) (1-20 micrograms/kg) dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, whereas i.v. administration of the L-type antagonist nicardipine (100 micrograms/kg), the P-type antagonist omega-agatoxin IVA (AgaTX) (20 micrograms/kg) or the OPQ family-type antagonist omega-conotoxin MVIIC (CmTX) (20 micrograms/kg) had no effect. However, CgTX (20 micrograms/kg) failed to inhibit substance P-induced guinea pig bronchoconstriction. CgTX (20 micrograms/kg) significantly inhibited cigarette smoke-induced guinea pig tracheal plasma extravasation, but not the substance P-induced reaction. CgTX also reduced electrical field stimulation-induced guinea pig bronchial smooth muscle contraction (0.01-10 microM) and capsaicin-induced substance P-like immunoreactivity release from guinea pig lung (0.14 microM). This evidence suggests that N-type Ca2+ channels modulate tachykinin release from capsaicin-sensitive afferent sensory nerve endings in guinea pig airway tissue.