Church J E, Hodgson W C
Deparment of Pharmacology, Monash University, Clayton, Victoria, Australia.
Toxicon. 2000 Mar;38(3):391-407. doi: 10.1016/s0041-0101(99)00169-5.
There has been recent debate regarding the labile nature of stonefish venoms and the pharmacology of their breakdown products. The present study examined the cardiovascular and neuromuscular effects of lyophilised venom, and conducted a preliminary investigation of freshly milked venom. Lyophilised venom (20 microg/ml) caused endothelium-dependent relaxation in rat aortae that was abolished by atropine (0.1 microM). In contrast, an endothelium-independent contractile response occurred in porcine coronary arteries. However, in the presence of atropine (10 nM), this became a relaxation response which was attenuated by the B2 antagonist FR-173657 (0.1 microM) or by a combination of idazoxan (1 microM) and propranolol (1 microM). In rat isolated atria, lyophilised venom (4 microg/ml) caused a biphasic inotropic response consisting of an initial decrease, and then increase, in force which were attenuated by atropine (0.5 microM) and propranolol (5 microM), respectively. The increase in force produced by venom was unaffected by reserpine pre-treatment suggesting a direct action at adrenoceptors. In the anaesthetised rat, lyophilised venom (1-300 microg/kg, i.v.), caused a dose-dependent depressor response, with a subsequent pressor response at higher concentrations (30-300 microg/kg, i.v.). In the presence of atropine (1 mg/kg, i.v.), the depressor response to venom was abolished, a transient pressor response unmasked and the secondary pressor response augmented. In the additional presence of prazosin (50 microg/kg, i.v.), the transient pressor response was abolished and the secondary pressor response attenuated. Lyophilised venom had no significant effect on nerve-evoked (10 microg/ml) or directly-evoked (100 microg/ml) twitches of the chick biventer cervicis muscle preparation. Milked venom (1 microl/ml) caused a biphasic response (i.e., an initial relaxation followed by contraction) in rat aortae, a contraction in porcine coronary arteries, complete cessation of rat isolated atrial activity and markedly inhibited both nerve-evoked and directly-evoked twitches of the chick biventer cervicis muscle preparation. In the anaesthetised rat, milked venom (15 microl/kg, i.v.) caused immediate cardiovascular collapse. It appears that the cardiovascular effects of stonefish venom are mediated by a dose-dependent action at muscarinic receptors and adrenoceptors.
最近，关于石鱼毒液的不稳定性质及其分解产物的药理学存在争议。本研究检测了冻干毒液对心血管和神经肌肉的影响，并对新鲜采集的毒液进行了初步研究。冻干毒液（20微克/毫升）可引起大鼠主动脉内皮依赖性舒张，该作用可被阿托品（0.1微摩尔）阻断。相反，在猪冠状动脉中则出现了非内皮依赖性收缩反应。然而，在存在阿托品（10纳摩尔）的情况下，该反应转变为舒张反应，且该舒张反应可被B2拮抗剂FR - 173657（0.1微摩尔）或咪唑克生（1微摩尔）与普萘洛尔（1微摩尔）的组合所减弱。在大鼠离体心房中，冻干毒液（4微克/毫升）引起双相变力反应，先是力的初始下降，然后增加，这两种反应分别被阿托品（0.5微摩尔）和普萘洛尔（5微摩尔）减弱。毒液产生的力增加不受利血平预处理的影响，提示其对肾上腺素能受体有直接作用。在麻醉大鼠中，冻干毒液（1 - 300微克/千克，静脉注射）引起剂量依赖性降压反应，在较高浓度（30 - 300微克/千克，静脉注射）时随后出现升压反应。在存在阿托品（1毫克/千克，静脉注射）的情况下，对毒液的降压反应被消除，短暂的升压反应被暴露，且继发性升压反应增强。在另外存在哌唑嗪（50微克/千克，静脉注射）的情况下，短暂的升压反应被消除，继发性升压反应减弱。冻干毒液对鸡双颈二腹肌标本的神经诱发（10微克/毫升）或直接诱发（100微克/毫升）的抽搐无显著影响。采集的毒液（1微升/毫升）在大鼠主动脉中引起双相反应（即先是舒张，随后收缩），在猪冠状动脉中引起收缩，使大鼠离体心房活动完全停止，并显著抑制鸡双颈二腹肌标本的神经诱发和直接诱发的抽搐。在麻醉大鼠中，采集的毒液（15微升/千克，静脉注射）引起立即的心血管衰竭。看来石鱼毒液的心血管作用是通过对毒蕈碱受体和肾上腺素能受体的剂量依赖性作用介导的。
