Effects of ω-Conotoxin GVIA on the Activation of Capsaicin-Sensitive Afferent Sensory Nerves in Guinea Pig Airway Tissues

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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 ω-conotoxin GVIA (CgTX) (1-20 μg/kg) dose-dependently inhibited capsaicin-induced guinea pig bronchoconstriction, whereas i.v. administration of the L-type antagonist nicardipine (100 μg/kg), the P-type antagonist ω-agatoxin IVA (AgaTX) (20 μg/kg) or the OPQ family-type antagonist ω-conotoxin MVIIC (CmTX) (20 μg/kg) had no effect. However, CgTX (20 μg/kg) failed to inhibit substance P-induced guinea pig bronchoconstriction. CgTX (20 μg/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 μM) and capsaicin-induced substance P-like immunoreactivity release from guinea pig lung (0.14 μM). This evidence suggests that N-type Ca²⁺ channels modulate tachykinin release from capsaicin-sensitive afferent sensory nerve endings in guinea pig airway tissue.