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新型巴西游走蛛毒素对大鼠皮质突触体中谷氨酸释放及胞内钙离子浓度的影响

Effects of new Phoneutria spider toxins on glutamate release and [Ca2+]i in rat cortical synaptosomes.

作者信息

Carneiro D S, Vieira L B, Cordeiro M N, Richardson M, Castro-Junior C J, Gomez M V, Reis H J

机构信息

Laboratório de Neurofarmacologia, Departamento de Farmacologia, ICB-UFMG. Av. Antônio Carlos, 6627. Campus Pampulha. BH-MG, CEP 31270-901, Brazil.

出版信息

Cell Mol Biol (Noisy-le-grand). 2010 Feb 9;56 Suppl:OL1223-30.

Abstract

Studies revealed that the venom of the Brazilian "armed" spider Phoneutria nigriventer contains potent neurotoxins that caused excitatory symptoms such as salivation, lachrymation, priapism, convulsions, flaccid and spastic paralysis. It was also reported that the main mechanism of action of those neurotoxins are effects on ion channels such as inhibition of the inactivation of Na+ channels, blockage of K+ channels and blockage of calcium channels. The venom from Phoneutria keyserlingi, as might be expected, contains a series of polypeptides that are very similar, but not identical, to the proteins previously obtained from the venom of P. nigriventer in terms of their amino acid sequences and biological activities. We evaluated the effects of some of the toxins of P. nigriventer and P. keyserlingi on glutamate release and the decrease in [Ca2+]i by using synaptosomes of rat brain cortices and fluorimetric assays. Sequence comparisons between the Phoneutria toxins of both the species showed great similarity in the location of cysteine residues. However, thus far, no pharmacological assays were performed to evaluate the extension of those biochemical modifications. Our results showed that differences between the amino acid sequences of Phoneutria toxins of both the species lead to the significant changes in the pharmacological properties of these toxins.

摘要

研究表明,巴西“武装”蜘蛛黑腹捕鸟蛛(Phoneutria nigriventer)的毒液含有强大的神经毒素,会引发兴奋症状,如流涎、流泪、阴茎异常勃起、抽搐、弛缓性和痉挛性麻痹。另据报道,这些神经毒素的主要作用机制是对离子通道产生影响,如抑制钠离子通道失活、阻断钾离子通道和阻断钙离子通道。不出所料,凯氏捕鸟蛛(Phoneutria keyserlingi)的毒液含有一系列多肽,这些多肽在氨基酸序列和生物活性方面与先前从黑腹捕鸟蛛毒液中获得的蛋白质非常相似,但并不完全相同。我们使用大鼠大脑皮质突触体和荧光测定法,评估了黑腹捕鸟蛛和凯氏捕鸟蛛的某些毒素对谷氨酸释放和细胞内钙离子浓度降低的影响。两种捕鸟蛛毒素之间的序列比较显示,半胱氨酸残基的位置具有高度相似性。然而,迄今为止,尚未进行药理学试验来评估这些生化修饰的程度。我们的结果表明,两种捕鸟蛛毒素的氨基酸序列差异导致了这些毒素药理特性的显著变化。

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