Omega-conotoxin GVIA specifically blocks neuronal mechanisms in rat ileum

Omega Conotoxin is a peptide venom of the marine snail Conus geographus which has been postulated as a neural specific calcium channel blocker in several systems. In the present study in rat ileum strips omega-conotoxin GVIA specifically blocked neuronal responses evoked by electrical field stimulation in a dose-dependent manner, but did not block responses induced by carbachol or direct depolarization with KCl. On the other hand the dyhydropyridine calcium channel blocker nitrendipine (10(-7) M) showed no specificity and blocked electrical field stimulation as well as carbachol- and KCl-induced contractions. This indicates that contractions of intestinal smooth muscle which can be blocked by dihydropyridine calcium channel blockers or Ca2+-free medium are not reduced by the neurotoxin omega-conotoxin. Omega-conotoxin caused even a little increase of the responses elicited by depolarisation with KCL. Omega-conotoxin blocked however neural mediated contractions which might suggest that it interacts with a distinct neuronal calcium channel and, in addition to tetrodotoxin, could provide a useful pharmacological tool to discriminate between muscular and neural sites of action of excitatory or inhibitory agents.