Okamoto M, Viskatis L J, de la Roza G, Vidal J C
Department of Pharmacology, Cornell University Medical College, New York, New York.
J Pharmacol Exp Ther. 1993 Apr;265(1):41-6.
Crotoxin, the major toxic component from the venom of Crotalus durissus terrificus is a potent neurotoxin (LD50, i.p., mice, 0.09 mg/kg) which possesses phospholipase A2 activity and causes a blockade of neuromuscular transmission. In this article, we show that mice injected daily with progressively increasing doses of crotoxin develop tolerance to the lethal action of this toxin. Treated mice tolerated daily doses of crotoxin 20- to 35-fold higher than the original LD50 without the characteristic signs of toxicity. Studies on the isolated phrenic nerve-diaphragm preparation in vitro from control (crotoxin-naive) mice showed that the exposure to 2 to 10 micrograms/ml crotoxin in the bath produced complete transmission blockade in 120 to 150 min. Conversely, the preparations from crotoxin-treated mice required crotoxin concentrations in the range of 17.5 to 100 micrograms/ml to produce complete neuromuscular block, being virtually insensitive during 200 min of exposure to 5 to 10 micrograms/ml crotoxin. Phrenic nerve-diaphragm preparations of control (crotoxin-naive) and crotoxin-treated mice did not show significant differences in sensitivity to the blocking action of carbamylcholine, suggesting that induction of tolerance to crotoxin is likely a presynaptic event.
响尾蛇毒素是南美巨蝮蛇毒液中的主要毒性成分，是一种强效神经毒素（腹腔注射，小鼠的半数致死量为0.09毫克/千克），具有磷脂酶A2活性，可导致神经肌肉传递阻滞。在本文中，我们表明，每天给小鼠注射剂量逐渐增加的响尾蛇毒素，小鼠会对这种毒素的致死作用产生耐受性。经过处理的小鼠能够耐受比原始半数致死量高20至35倍的响尾蛇毒素日剂量，且没有明显的毒性迹象。对来自对照（未接触过响尾蛇毒素）小鼠的离体膈神经 - 膈肌标本的研究表明，在浴槽中暴露于2至10微克/毫升的响尾蛇毒素会在120至150分钟内产生完全的传递阻滞。相反，来自经响尾蛇毒素处理的小鼠的标本需要17.5至100微克/毫升范围内的响尾蛇毒素浓度才能产生完全的神经肌肉阻滞，在暴露于5至10微克/毫升响尾蛇毒素的200分钟内几乎不敏感。对照（未接触过响尾蛇毒素）和经响尾蛇毒素处理的小鼠的膈神经 - 膈肌标本对氨甲酰胆碱的阻滞作用的敏感性没有显著差异，这表明对响尾蛇毒素耐受性的诱导可能是一个突触前事件。
