Rash L D, Birinyi-Strachan L C, Nicholson G M, Hodgson W C
Monash Venom Group, Department of Pharmacology, Monash University, Clayton, Victoria 3168, Australia.
Br J Pharmacol. 2000 Aug;130(8):1817-24. doi: 10.1038/sj.bjp.0703494.
Mouse spiders represent a potential cause of serious envenomation in humans. This study examined the activity of Missulena bradleyi venom in several in vitro preparations. Whilst female M. bradleyi venom at doses up to 0.05 microl ml(-1) failed to alter twitch or resting tension in all preparations used, male venom (0.02 and 0.05 microl ml(-1)) produced potent effects on transmitter release in both smooth and skeletal neuromuscular preparations. In the mouse phrenic nerve diaphragm preparation, male M. bradleyi venom (0.02 microl ml(-1)) caused rapid fasciculations and an increase in indirectly evoked twitches. Male venom (0.02 and 0.05 microl ml(-1)) also caused a large contracture and rapid decrease in indirectly evoked twitches in the chick biventer cervicis muscle, however had no effect on responses to exogenous ACh (1 mM) or potassium chloride (40 mM). In the chick preparation, contractile responses to male M. bradleyi venom (0.05 microl ml(-1)) were attenuated by (+)-tubocurarine (100 microM) and by tetrodotoxin (TTX, 1 microM). Both actions of male M. bradleyi venom were blocked by Atrax robustus antivenom (2 units ml(-1)). In the unstimulated rat vas deferens, male venom (0.05 microl ml(-1)) caused contractions which were inhibited by a combination of prazosin (0.3 microM) and P(2X)-receptor desensitization (with alpha,beta-methylene ATP 10 microM). In the rat stimulated vas deferens, male venom (0.05 microl ml(-1)) augmented indirectly evoked twitches. Male venom (0.1 microl ml(-1)) causes a slowing of inactivation of TTX-sensitive sodium currents in acutely dissociated rat dorsal root ganglion neurons. These results suggest that venom from male M. bradleyi contains a potent neurotoxin which facilitates neurotransmitter release by modifying TTX-sensitive sodium channel gating. This action is similar to that of the delta-atracotoxins from Australian funnel-web spiders.
鼠蛛是人类严重中毒的一个潜在原因。本研究检测了布拉德利鼠蛛毒液在几种体外制剂中的活性。虽然雌性布拉德利鼠蛛毒液剂量高达0.05微升/毫升时，在所使用的所有制剂中均未改变抽搐或静息张力，但雄性毒液（0.02和0.05微升/毫升）在平滑肌和骨骼肌神经肌肉制剂中对递质释放均产生了显著影响。在小鼠膈神经膈肌制剂中，雄性布拉德利鼠蛛毒液（0.02微升/毫升）引起快速肌束颤动，并使间接诱发的抽搐增加。雄性毒液（0.02和0.05微升/毫升）在鸡的二腹肌颈肌中也引起了大的挛缩，并使间接诱发的抽搐迅速减少，然而对外源性乙酰胆碱（1毫摩尔）或氯化钾（40毫摩尔）的反应没有影响。在鸡的制剂中，对雄性布拉德利鼠蛛毒液（0.05微升/毫升）的收缩反应被筒箭毒碱（100微摩尔）和河豚毒素（TTX，1微摩尔）减弱。雄性布拉德利鼠蛛毒液的这两种作用均被粗壮漏斗蛛抗毒血清（2单位/毫升）阻断。在未受刺激的大鼠输精管中，雄性毒液（0.05微升/毫升）引起收缩，这被哌唑嗪（0.3微摩尔）和P2X受体脱敏（用α，β-亚甲基ATP 10微摩尔）的联合作用所抑制。在受刺激的大鼠输精管中，雄性毒液（0.05微升/毫升）增强了间接诱发的抽搐。雄性毒液（0.1微升/毫升）使急性分离的大鼠背根神经节神经元中TTX敏感的钠电流失活减慢。这些结果表明，雄性布拉德利鼠蛛的毒液含有一种强效神经毒素，它通过改变TTX敏感的钠通道门控来促进神经递质释放。这种作用与澳大利亚漏斗网蜘蛛的δ-atra毒素相似。
