Lumsden Natalie G, Fry Bryan G, Ventura Sabatino, Kini R Manjunatha, Hodgson Wayne C
Monash Venom Group, Department of Pharmacology, Monash University, Clayton Vic. 3800, Australia.
Toxicon. 2005 Mar 1;45(3):329-34. doi: 10.1016/j.toxicon.2004.11.003. Epub 2005 Jan 20.
In this study, we have pharmacologically characterised boigatoxin-A, a three finger toxin isolated from the venom of the colubrid, Boiga dendrophila (Mangrove catsnake). In the chick biventer cervicis nerve-muscle preparation boigatoxin-A (1 microM) displayed poorly reversible postsynaptic blockade as evidenced by the inhibition of indirect (0.1 Hz, 0.2 ms, supramaximal V) twitches and responses to exogenous acetylcholine (1 mM) and carbachol (20 microM). Boigatoxin-A (0.3-0.5 microM) caused a concentration-dependent depression of the maximum response of cumulative concentration response curves to CCh (0.6-80 microM). Boigatoxin-A (1 microM) induced readily reversible inhibition of electrically evoked (0.2 Hz, 0.3 ms, 70-100 V) twitches of the prostatic segment of the rat vas deferens. This inhibition was not significantly attenuated by 8-phenyltheophylline (20 microM) or idazoxan (1 microM). Boigatoxin-A (1 microM) did not affect alpha,beta-mATP (10 microM) or noradrenaline (25 microM) responses in unstimulated epididymal segments of the rat vas deferens. Our data suggests that this toxin has weak postsynaptic neurotoxicity in skeletal muscle and also prejunctional neurotoxic activity in the smooth muscle of the rat vas deferens to inhibit the release of neurotransmitter(s), but not via prejunctional purinergic or adrenergic receptors. This is the first report of such activity for a toxin isolated from snake venom and reinforces the largely untapped potential of colubrid venoms.
在本研究中,我们对从游蛇科(Boiga dendrophila,红树林猫蛇)毒液中分离出的三指毒素——波加毒素 - A进行了药理学特性分析。在鸡颈二腹肌神经 - 肌肉标本中,波加毒素 - A(1微摩尔)表现出可逆性较差的突触后阻断作用,这可通过对间接(0.1赫兹,0.2毫秒,超强电压)抽搐以及对外源性乙酰胆碱(1毫摩尔)和卡巴胆碱(20微摩尔)的反应受到抑制得以证明。波加毒素 - A(0.3 - 0.5微摩尔)导致对氯化乙酰胆碱(0.6 - 80微摩尔)累积浓度反应曲线的最大反应呈浓度依赖性降低。波加毒素 - A(1微摩尔)可诱导大鼠输精管前列腺段电诱发(0.2赫兹,0.3毫秒,70 - 100伏)抽搐的快速可逆性抑制。这种抑制作用并未被8 - 苯基茶碱(20微摩尔)或咪唑克生(1微摩尔)显著减弱。波加毒素 - A(1微摩尔)对未受刺激的大鼠输精管附睾段中的α,β - 甲基ATP(10微摩尔)或去甲肾上腺素(25微摩尔)反应没有影响。我们的数据表明,这种毒素在骨骼肌中具有较弱的突触后神经毒性,在大鼠输精管平滑肌中也具有突触前神经毒性活性,可抑制神经递质的释放,但不是通过突触前嘌呤能或肾上腺素能受体。这是关于从蛇毒中分离出的毒素具有此类活性的首次报道,也强化了游蛇科毒液在很大程度上尚未开发的潜力。