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.
Allescher
H D
HD
Department of Internal Medicine, II, Technical University of Munich, West Germany.
Willis
S
S
Schusdziarra
V
V
Classen
M
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009568:Nitrendipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008978:Mollusk Venoms; D013779:Tetrodotoxin; D002217:Carbachol; D020866:omega-Conotoxin GVIA; D009568:Nitrendipine