Bell K L, Sutherland S K, Hodgson W C
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Toxicon. 1998 Jan;36(1):63-74. doi: 10.1016/s0041-0101(97)00060-3.
The present study was designed to obtain a basic pharmacological profile of venom from the inland taipan (Oxyuranus microlepidotus). Venom (0.05-50 micrograms/ml) produced dose-dependent contractions in guinea-pig ileum, which could not be reproduced upon second administration. The cyclooxygenase inhibitor indomethacin (1 microM), a preceding anaphylactic response induced by egg albumin and inactivation of phospholipase A2 (PLA2) by incubation with 4-bromophenacyl bromide (1.8 mM) all significantly inhibited responses to venom (0.5 micrograms/ml). Venom (0.5 micrograms/ml) caused inhibition of stimulation-induced contractions in the prostatic segment of rat vas deferens which was not significantly affected by the alpha 2-adrenoceptor antagonist idazoxan (0.3 microM). Venom (10 micrograms/ml) caused time-dependent inhibition of the rat electrically stimulated phrenic nerve-diaphragm preparation, positive inotropic and chronotropic responses in rat isolated atria and relaxation in rat endothelium-denuded and -intact isolated aortae. In endothelium-intact aortae, the nitric oxide synthase inhibitor N-nitro-L-arginine (NOLA, 0.1 mM) significantly inhibited the response to venom (10 micrograms/ml). Venom (50 micrograms/kg, i.v.) caused an immediate drop in blood pressure followed by cardiovascular collapse in anaesthetised rats. Venom (10 micrograms/kg, i.v.) caused a gradual fall in blood pressure which was sometimes accompanied by a temporary cessation of respiration. A PLA2 assay detected the presence of PLA2 in the venom. These results suggest that the venom contains a component capable of causing the synthesis of arachidonic acid metabolites and a component capable of relaxing vascular smooth muscle. The inhibitory effect on the phrenic nerve-diaphragm is probably due to the previously identified neurotoxin (paradoxin).
本研究旨在获得内陆太攀蛇（Oxyuranus microlepidotus）毒液的基本药理学特征。毒液（0.05 - 50微克/毫升）在豚鼠回肠中产生剂量依赖性收缩，再次给药时无法重现这种收缩。环氧化酶抑制剂吲哚美辛（1微摩尔/升）、卵清蛋白诱导的先前过敏反应以及与4 - 溴苯甲酰溴（1.8毫摩尔/升）孵育使磷脂酶A2（PLA2）失活，均显著抑制对毒液（0.5微克/毫升）的反应。毒液（0.5微克/毫升）抑制大鼠输精管前列腺段的刺激诱导收缩，α2肾上腺素能受体拮抗剂咪唑克生（0.3微摩尔/升）对此无显著影响。毒液（10微克/毫升）对大鼠电刺激膈神经 - 膈肌标本产生时间依赖性抑制，对大鼠离体心房产生正性变力和变时反应，对大鼠去内皮和完整离体主动脉产生舒张作用。在完整内皮的主动脉中，一氧化氮合酶抑制剂N - 硝基 - L - 精氨酸（NOLA，0.1毫摩尔/升）显著抑制对毒液（10微克/毫升）的反应。毒液（50微克/千克，静脉注射）使麻醉大鼠血压立即下降，随后出现心血管衰竭。毒液（10微克/千克，静脉注射）使血压逐渐下降，有时伴有呼吸暂时停止。PLA2检测表明毒液中存在PLA2。这些结果表明，该毒液含有一种能够引起花生四烯酸代谢物合成的成分和一种能够舒张血管平滑肌的成分。对膈神经 - 膈肌的抑制作用可能归因于先前鉴定出的神经毒素（paradoxin）。
