Azuma H, Ishikawa M, Nakajima T, Satoh A, Sekizaki S
Br J Pharmacol. 1986 Jul;88(3):549-59. doi: 10.1111/j.1476-5381.1986.tb10235.x.
The purpose of the present experiments was to investigate the pharmacological mechanisms of the vasoconstriction caused by the toxin (pCrTX) which had been partially purified from the tentacles of the jellyfish Carybdea rastonii ('Andonkurage'). pCrTX (0.1 to 10 micrograms ml-1) produced a tonic contraction of rabbit aortic strips, which was nearly abolished in Ca2+-free medium and was significantly reduced by verapamil or diltiazem. pCrTX stimulated 45Ca2+-influx and this effect was markedly attenuated by verapamil. pCrTX-induced vasoconstriction was significantly attenuated by phentolamine, 6-hydroxydopamine (6-OHDA) and in low Na+-medium, but not by bretylium, guanethidine, reserpinization or tetrodotoxin (TTX). pCrTX continuously and significantly increased the 3H-efflux from [3H]-noradrenaline preloaded aortic strips and this effect was completely inhibited by pretreatment with 6-OHDA and in Ca2+-free medium, but not by phentolamine, bretylium, guanethidine or TTX. A single exposure to pCrTX for 30 min greatly reduced the contractile responses to tyramine, nicotine and transmural electrical stimulation, but not those to noradrenaline or KC1. In addition, incorporation of [3H]-noradrenaline was reduced. Pretreatments with chlorphenylamine or indomethacin failed to modify the contractile response to pCrTX. These results suggest that the pCrTX-induced vasoconstriction is caused by a presynaptic action, releasing noradrenaline from the intramural adrenergic nerve terminals, and by a postsynaptic action, which consists at least in part of stimulation of the transmembrane calcium influx. Both pre- and postsynaptic actions depend on the external calcium concentration. The data further suggest that pCrTX damages the noradrenaline uptake and/or storage mechanisms without damaging postsynaptic contractile systems.
本实验的目的是研究从僧帽水母（“安德库拉吉”）触手部分纯化得到的毒素（pCrTX）引起血管收缩的药理机制。pCrTX（0.1至10微克/毫升）可使兔主动脉条产生强直性收缩，在无钙培养基中这种收缩几乎消失，且维拉帕米或地尔硫卓可使其明显减弱。pCrTX刺激45Ca2+内流，而维拉帕米可显著减弱这种作用。酚妥拉明、6-羟基多巴胺（6-OHDA）以及在低钠培养基中可使pCrTX诱导的血管收缩明显减弱，但溴苄铵、胍乙啶、利血平化或河豚毒素（TTX）则无此作用。pCrTX持续且显著增加[3H]-去甲肾上腺素预负荷的主动脉条的3H外流，6-OHDA预处理以及在无钙培养基中可完全抑制这种作用，但酚妥拉明、溴苄铵、胍乙啶或TTX则无此作用。单次暴露于pCrTX 30分钟可大大降低对酪胺、尼古丁和跨壁电刺激的收缩反应，但对去甲肾上腺素或氯化钾则无此作用。此外，[3H]-去甲肾上腺素的摄取减少。氯苯那敏或吲哚美辛预处理未能改变对pCrTX的收缩反应。这些结果表明，pCrTX诱导的血管收缩是由突触前作用引起的，即从壁内肾上腺素能神经末梢释放去甲肾上腺素，以及由突触后作用引起的，突触后作用至少部分包括刺激跨膜钙内流。突触前和突触后作用均取决于细胞外钙浓度。数据还表明，pCrTX损害去甲肾上腺素摄取和/或储存机制，但不损害突触后收缩系统。
