Effect of omega-conotoxin GVIA on tetrodotoxin-insensitive acetylcholine release by nicotine in guinea-pig bladder.
1. Contractile responses and acetylcholine release evoked by nicotine and electrical field stimulation (EFS) were determined by isotonic transducer and radioimmunoassay, respectively. 2. Nicotine-induced contraction was reduced to 30% by nicotinic receptor antagonist, hexamethonium but was insensitive to tetrodotoxin. EFS-induced contraction was abolished by tetrodotoxin but was insensitive to hexamethonium. Replacement of external Na by choline completely abolished the contractile responses evoked by nicotine and EFS. 3. Both contractions evoked by nicotine and EFS were inhibited by omega-conotoxin GVIA, and inhibitory effects of the toxin were greater in low Ca concentrations. 4. In the condition that external Na or Ca is omitted from physiological solution, acetylcholine release evoked by nicotine was not observed. Nicotine-induced acetylcholine release was partially inhibited by omega-conotoxin but was insensitive to tetrodotoxin. 5. In conclusion, nicotine interacts with nicotinic receptors located on nerve terminals and produces transmitter release which depends on external Na through tetrodotoxin-insensitive mechanisms. It is suggested that voltage-dependent omega-conotoxin sensitive Ca channels are partially involved in the nicotine-induced transmitter release.
Shinkai
M
M
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Takayanagi
I
I
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects; D012964:Sodium / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D006584:Hexamethonium Compounds; D010455:Peptides; D011978:Receptors, Nicotinic; D013779:Tetrodotoxin; D009538:Nicotine; D002217:Carbachol; D020866:omega-Conotoxin GVIA; D012964:Sodium; D000109:Acetylcholine; D002118:Calcium