Lumsden N G, Fry B G, Ventura S, Kini R M, Hodgson W C
Monash Venom Group, Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia.
Auton Autacoid Pharmacol. 2004 Oct;24(4):107-13. doi: 10.1111/j.1474-8673.2004.00322.x.
The great taxonomic and prey base diversity of colubrids (non-front-fanged snakes) suggests that their venoms may represent a 'literal gold mine' for scientists eager to find novel pharmacological probes. While pharmacological characterization is lacking for most of these venoms, this is even more so with regard to activity of colubrid venoms on the mammalian autonomic nervous system. This study characterizes the activity of venom from the colubrid, Boiga dendrophila using in vitro smooth muscle preparations and the anaesthetized rat. In the prostatic segment of the rat vas deferens, cumulative additions of venom (1-150 microg ml(-1)) induced concentration-dependent inhibition of electrically evoked (0.2 Hz, 0.3 ms, 70-100 V) twitches. The inhibitory effect of venom (100 microg ml(-1)) was attenuated by 8-phenyltheophylline (8-PT) (20 microM) and 8-cyclopentyl-1, 3-dipropylxanthine (20 microM) but not idazoxan (1 microM), or a combination of ranitidine (0.2 microM) and thioperamide (10 microM). The inhibitory effect of venom (100 microg ml(-1)) was augmented by dipyridamole (10 microM) but abolished by pretreatment with adenosine deaminase (7.5 units/100 microl) suggesting that it contains components with adenosine A(1) receptor activity, most likely adenosine. In isolated segments of guinea-pig ileum, venom (10-100 microg ml(-1)) caused concentration-dependent contractions which were inhibited by the muscarinic receptor antagonist atropine (0.1 microM) but not by the histamine receptor antagonist mepyramine (0.5 microM). In the anaesthetized rat, venom (5-7.5 mg kg(-1), i.v.) caused a hypotensive effect. Our data suggest that the venom contains components with purinergic and muscarinic receptor activity.
黄颌蛇科(无毒牙的蛇类)在分类学和猎物基础方面具有高度的多样性,这表明它们的毒液对于渴望找到新型药理学探针的科学家而言,可能是一座“名副其实的金矿”。尽管这些毒液大多缺乏药理学特征描述,但黄颌蛇科毒液对哺乳动物自主神经系统的活性更是如此。本研究利用体外平滑肌制备物和麻醉大鼠,对黄颌蛇科的绞花林蛇毒液的活性进行了表征。在大鼠输精管的前列腺段,累积添加毒液(1 - 150微克/毫升)可引起电诱发(0.2赫兹,0.3毫秒,70 - 100伏)抽搐的浓度依赖性抑制。毒液(100微克/毫升)的抑制作用可被8 - 苯基茶碱(8 - PT)(20微摩尔)和8 - 环戊基 - 1,3 - 二丙基黄嘌呤(20微摩尔)减弱,但不受咪唑克生(1微摩尔)或雷尼替丁(0.2微摩尔)与硫代哌酰胺(10微摩尔)组合的影响。毒液(100微克/毫升)的抑制作用可被双嘧达莫(10微摩尔)增强,但在用腺苷脱氨酶(7.5单位/100微升)预处理后被消除,这表明它含有具有腺苷A(1)受体活性的成分,很可能是腺苷。在豚鼠回肠的离体段,毒液(10 - 100微克/毫升)引起浓度依赖性收缩,这种收缩可被毒蕈碱受体拮抗剂阿托品(0.1微摩尔)抑制,但不受组胺受体拮抗剂美吡拉敏(0.5微摩尔)抑制。在麻醉大鼠中,毒液(5 - 7.5毫克/千克,静脉注射)引起降压作用。我们的数据表明,该毒液含有具有嘌呤能和毒蕈碱受体活性的成分。