Differential effects of omega-conotoxin GVIA and tetrodotoxin on vasoconstrictions evoked by electrical stimulation and nicotinic receptor stimulation in canine isolated, perfused splenic arteries.
1. The effects of omega-conotoxin GVIA (omega-CgTX) and tetrodotoxin (TTX) on vasoconstrictions induced by acetylcholine (ACh) and nicotine were investigated and compared with those induced by periarterial electrical stimulation in the isolated and perfused canine splenic arteries. 2. ACh and nicotine at doses of 0.01 to 1 mumol constricted the splenic artery, dose-dependently. ACh induced consistent responses, but the vasoconstrictor responses to nicotine became significantly smaller with repeated administration of nicotine. 3. Periarterial electrical stimulation produced a vasoconstriction that was abolished by either TTX (30 nmol) or omega-CgTX (3 nmol), but the vasoconstrictor response to nicotine was not significantly affected by the same doses of TTX and omega-CgTX. Inhibitions by TTX and omega-CgTX of ACh-induced vasoconstrictions were small but statistically significant, showing that the percentage inhibition was less than 15%. TTX and omega-CgTX did not affect the vasoconstrictor responses to exogenous noradrenaline (NA). 4. ACh did not produce any vasoconstriction in the preparations treated either with alpha-adrenoceptor antagonists (10 microM bunazosin and 10 microM midaglizole) or with 30 microM guanethidine. NA-induced responses were abolished by alpha-adrenoceptor antagonists, but not affected by guanethidine treatment. 5. Vascular responses to ACh were completely inhibited by 1 mumol hexamethonium. In the preparations treated with 100 nmol nicotine, ACh did not produce any vasoconstriction. However, the NA-induced vasoconstriction was affected by neither hexamethonium nor nicotine treatment. 6. Atropine (1 microM) significantly inhibited but did not abolish the vasoconstrictor responses to ACh. The vascular responses to nicotine and NA were also significantly inhibited by atropine treatment. 7. These results indicate that (1) ACh constricts the splenic artery through the activation of presynaptic nicotinic receptors present on the sympathetic nerves; (2) differential effects of TTX and omega-CgTX on the vascular responses to ACh and nicotine, and to electrical stimulation suggest that the receptor-operated ion channels are mainly responsible for NA release induced by nicotinic receptor stimulation, but N-type VOCCs are responsible for that by electrical stimulation; (3) atropine may have an inhibitory action on nicotine-related responses, in addition to its inhibitory action on NA.
Ren
L M
LM
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Nakane
T
T
Chiba
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010477:Perfusion; D011978:Receptors, Nicotinic / Q000502:physiology*; D013157:Splenic Artery / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D020866:omega-Conotoxin GVIA
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D006584:Hexamethonium Compounds; D010455:Peptides; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D013779:Tetrodotoxin; D009538:Nicotine; D020866:omega-Conotoxin GVIA; D000109:Acetylcholine; D006145:Guanethidine