Omega-conotoxin-sensitive calcium channels modulate autonomic neurotransmission in guinea pig airways

omega-Conotoxin GVIA, a peptide derived from the marine snail Conus geographus, is an antagonist of the neuronal N type voltage-sensitive calcium channels associated with neurotransmitter release. The present study investigated effects of this peptide on neurally mediated responses in airways isolated from the guinea pig to determine whether airway nerves are modulated by omega-conotoxin-sensitive calcium channels. Electrical field stimulation was used to induce neurally mediated tachykininergic excitatory responses in guinea pig bronchus and cholinergic excitatory and nonadrenergic noncholinergic inhibitory responses in guinea pig trachea. Exogenous agonists were administered to induce contractile (acetylcholine, substance P) or relaxation (sodium nitroprusside) responses. Tissues were incubated with omega-conotoxin (1 microM) or its vehicle (10 mM acetic acid) for 30 min before establishing frequency- or concentration-response relationships to the various stimuli. Frequency-response curves for neurally mediated cholinergic, nonadrenergic nocholinergic inhibitory and tachykininergic responses were shifted to the right by omega-conotoxin to a similar extent (4- to 5-fold). omega-Conotoxin had no effect on contractile responses elicited by exogenous acetylcholine or substance P or on relaxations induced by sodium nitroprusside. These findings indicate that neurotransmission in afferent tachykininergic kininergic nerves and in efferent cholinergic excitatory and nonadrenergic noncholinergic inhibitory nerves in the airways is modulated by a prejunctional omega-conotoxin-sensitive mechanism.