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矛头蝮蛇血浆中的激肽释放酶-激肽系统。

Kallikrein-kinin system in the plasma of the snake Bothrops jararaca.

作者信息

Abdalla F M, Hiraichi E, Picarelli Z P, Prezoto B C

机构信息

Servico de Farmacologia, Instituto Butantan Av. Dr. Vital Brazil, Sö Paulo.

出版信息

Br J Pharmacol. 1989 Sep;98(1):252-8. doi: 10.1111/j.1476-5381.1989.tb16889.x.

Abstract
  1. Bothrops jararaca venom (BJV) caused a fall in the carotid artery blood pressure of the anaesthetized snake. This effect was tachyphylactic and was potentiated by captopril, a kininase II inhibitor; it was partially antagonized by promethazine plus cimetidine and was not affected by atropine. 2. Similar hypotensive effects were obtained by administration of trypsin or a partially purified BJV kininogenase to the snake. 3. Incubation of Bothrops jararaca plasma (BJP) with trypsin released a substance (or substances) that produced hypotension in the snake but not in the rat; this hypotensive effect was also potentiated by captopril. 4. The trypsinised plasma contracted Bothrops jararaca isolated uterus, a pharmacological preparation weakly sensitive to bradykinin. Trypsinised plasma was inactive on pigeon oviduct and rat uterus and displayed a weak action on the guinea-pig ileum. Similar effects were observed with incubates of a fraction of BJP, containing globulins, with a partially purified BJV kininogenase. 5. Like mammalian kinins, the substance(s) was(were) dialysable, thermostable in acid but not in alkaline pH, and inactivated by chymotrypsin but not by trypsin. Its(their) inactivation by BJP or BJP kininase II was inhibited by captopril. 6. These findings strongly suggest that, besides releasing histamine, BJV or trypsin release a kininlike substance (or substances) from the snake plasma. 7. Since BJV and other kininogenases active on mammalian plasma were shown to be unable to release kinins from BJP, in experiments conducted on pharmacological preparations suitable for the assay of mammalian kinins, these data also suggest that the snake Bothrops jararaca, like birds, may have developed its own kallikrein-kinin system.
摘要
  1. 巴西矛头蝮蛇毒(BJV)可使麻醉状态下的蛇的颈动脉血压下降。这种效应具有快速耐受性,且被激肽酶II抑制剂卡托普利增强;它被异丙嗪加西咪替丁部分拮抗,且不受阿托品影响。2. 给蛇注射胰蛋白酶或部分纯化的BJV激肽原酶可获得类似的降压效果。3. 用胰蛋白酶孵育巴西矛头蝮蛇血浆(BJP)可释放一种(或多种)物质,该物质能使蛇血压降低,但对大鼠无此作用;这种降压效应也被卡托普利增强。4. 经胰蛋白酶处理的血浆可使巴西矛头蝮蛇离体子宫收缩,该药理制剂对缓激肽敏感性较弱。经胰蛋白酶处理的血浆对鸽输卵管和大鼠子宫无活性,对豚鼠回肠作用较弱。用含有球蛋白的BJP组分与部分纯化的BJV激肽原酶的孵育物也观察到类似效应。5. 与哺乳动物激肽一样,该物质(或这些物质)可透析,在酸性条件下热稳定但在碱性pH条件下不稳定,且被糜蛋白酶灭活但不被胰蛋白酶灭活。其(它们的)被BJP或BJP激肽酶II灭活的过程被卡托普利抑制。6. 这些发现强烈表明,除了释放组胺外,BJV或胰蛋白酶还从蛇血浆中释放出一种类激肽物质(或多种物质)。7. 由于在适用于检测哺乳动物激肽的药理制剂实验中表明,BJV和其他对哺乳动物血浆有活性的激肽原酶无法从BJP中释放激肽,这些数据还表明,蛇巴西矛头蝮蛇可能像鸟类一样,已经发展出了自己的激肽释放酶-激肽系统。

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