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 respira tory reactions induced by the activation of capsaicin-sensitive affere nt sensory nerves. Intravenous (i.v.) injection of the N-type Ca2+ cha nnel antagonist omega-conotoxin GVIA (CgTX) (1-20 mu g/kg) dose-depend ently inhibited capsaicin-induced guinea pig bronchoconstriction, wher eas i.v. administration of the L-type antagonist nicardipine (100 mu g /kg), the P-type antagonist omega-agatoxin IVA (AgaTX) (20 mu g/kg) or the OPQ family-type antagonist omega-conotoxin MVIIC (CmTX) (20 mu g/ kg) had no effect. However, CgTX (20 mu g/kg) failed to inhibit substa nce P-induced guinea pig bronchoconstriction. CgTX (20 mu g/kg) signif icantly inhibited cigarette smoke-induced guinea pig tracheal plasma e xtravasation, but not the substance P-induced reaction. CgTX also redu ced electrical field stimulation-induced guinea pig bronchial smooth m uscle contraction (0.01-10 mu M) and capsaicin-induced substance P-lik e immunoreactivity release from guinea pig lung (0.14 mu M). This evid ence suggests that N-type Ca2+ channels modulate tachykinin release fr om capsaicin-sensitive afferent sensory nerve endings in guinea pig ai rway tissue.