Gwee M C, Wong P T, Gopalakrishnakone P, Cheah L S, Low K S
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
Toxicon. 1993 Oct;31(10):1305-14. doi: 10.1016/0041-0101(93)90403-6.
Documentation on the biological activity (including the lethality) of the venom (BSV) from the black scorpion Heterometrus longimanus is lacking. We have investigated the effects of BSV on adrenergic transmission using the rat isolated anococcygeus muscle (Acm), since the venom from several species of scorpions causes peripheral sympathetic nerve stimulation with enhanced adrenergic responses. The catecholamine content in BSV was also measured by HPLC. The effects of phentolamine (5 microM), guanethidine (5 microM), desipramine (1.5 microM), tetrodotoxin (2 microM) and reserpine pretreatment in vivo (5 mg/kg s.c. x 24 hr and 5 mg/kg i.p. x 3 hr) on contractile responses of the rat Acm to field stimulation, crude BSV (2-10 microliters in 6 ml bath), noradrenaline (3 microM), tyramine (10-15 microM), carbachol (2-3 microM) and potassium chloride (50-75 mM) were investigated. BSV mimicked the agonist actions of noradrenaline (NA) by acting directly on postjunctional alpha-adrenoceptors in the anococcygeus muscle. The LD50 of crude BSV injected i.v. into mice was 0.13 ml per kg mouse. Sequential ultrafiltration of the crude BSV revealed the presence of a substance of low mol. wt which mediates the postjunctional alpha-agonist actions of BSV. HPLC measurements confirmed the presence of noradrenaline (NA; mean concentration of 1.8 +/- 0.3 mM) in BSV; the dopamine concentration (mean of 31 +/- 4 microM) was 60-fold lower than that of NA, whereas adrenaline was not detected in all the 15 samples investigated. Thus, the presence of NA in BSV can account for the postjunctional alpha-agonist actions of the venom in the Acm.
关于长掌异蝎毒液(BSV)的生物活性(包括致死性)的文献资料尚缺。我们使用大鼠离体肛门尾骨肌(Acm)研究了BSV对肾上腺素能传递的影响,因为几种蝎子的毒液会引起外周交感神经刺激并增强肾上腺素能反应。还通过高效液相色谱法测量了BSV中的儿茶酚胺含量。研究了酚妥拉明(5微摩尔)、胍乙啶(5微摩尔)、地昔帕明(1.5微摩尔)、河豚毒素(2微摩尔)以及体内利血平预处理(5毫克/千克皮下注射×24小时和5毫克/千克腹腔注射×3小时)对大鼠Acm对场刺激、粗制BSV(6毫升浴槽中2 - 10微升)、去甲肾上腺素(3微摩尔)、酪胺(10 - 15微摩尔)、卡巴胆碱(2 - 3微摩尔)和氯化钾(50 - 75毫摩尔)收缩反应的影响。BSV通过直接作用于肛门尾骨肌的节后α - 肾上腺素能受体模拟了去甲肾上腺素(NA)的激动剂作用。静脉注射粗制BSV至小鼠的半数致死量为每千克小鼠0.13毫升。对粗制BSV进行连续超滤显示存在一种低分子量物质,该物质介导了BSV的节后α - 激动剂作用。高效液相色谱测量证实BSV中存在去甲肾上腺素(NA;平均浓度为1.8±0.3毫摩尔);多巴胺浓度(平均为31±4微摩尔)比NA低60倍,而在所研究的全部15个样品中均未检测到肾上腺素。因此,BSV中NA的存在可以解释该毒液在Acm中的节后α - 激动剂作用。