Differential effects of ω‐conotoxin GVIA and tetrodotoxin on vasoconstrictions evoked by electrical stimulation and nicotinic receptor stimulation in canine isolated, perfused splenic arteries

Abstract

1 The effects of w-conotoxin GVIA (Qo-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. 5 Vascular responses to ACh were completely inhibited by 1 pmol 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 ftM) 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 w-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.

Tetrodotoxin alleviates acute heroin withdrawal syndrome: A multicentre, randomized, double-blind, placebo-controlled study

“…29 TTX is a reversible selective inhibitor of sodium channel conductance, 6,7 which can block nerve conduction, which in turn effects the efficiency of transmitter release. 30,31 We have a hypothesis that the efficacy of TTX in attenuating the severity of acute withdrawal syndrome might be as a result of these effects on peripheral sodium channels. However, although the present results support the finding that TTX can alleviate acute heroin withdrawal syndrome, more preclinical research is required to describe the exact mechanism by which this occurs.…”

Differential Blocking Effects of Tetrodotoxin on Double‐peaked Vasoconstrictor Responses to Periarterial Nerve Stimulation in Canine Isolated, Perfused Splenic Artery

“…7-10 Ren et al 14,15 have also reported that 30 nmol/L TTX completely inhibits vasoconstrictor responses to periarterial nerve stimulation in canine splenic artery. 7-10 Ren et al 14,15 have also reported that 30 nmol/L TTX completely inhibits vasoconstrictor responses to periarterial nerve stimulation in canine splenic artery.…”

Effects of ω‐conotoxin GVIA and diltiazem on double peaked vasoconstrictor responses to periarterial electric nerve stimulation in isolated canine splenic artery

“…The depolarization‐induced release of neurotransmitters is dependent upon a prejunctional influx of extra‐cellular calcium ions through voltage‐gated calcium channels (VGCCs) (Mulkey & Zucker, 1991). N‐type VGCCs have been shown to play a key role in triggering neurotransmitter release from sympathetic nerve terminals (Maggi et al ., 1988; De Luca et al ., 1990; Pruneau & Angus, 1990; Fabi et al ., 1993; Ren et al ., 1994; Wright & Angus, 1996). Since adenosine 5′‐triphosphate (ATP) has been proposed as a co‐transmitter with noradrenaline in peripheral sympathetic nervous system (Burnstock, 1972; 1979; 1988), an interesting point raised is whether the release of the two co‐transmitters are subject to parallel modulation by N‐type VGCCs.…”