Fozard J R, Mwaluko G M
Br J Pharmacol. 1976 May;57(1):115-25. doi: 10.1111/j.1476-5381.1976.tb07661.x.
1 Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5-hydroxytryptamine (5-HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethylphenylpiperazinium (DMPP). 2 The cardiac stimulant effects of 5-HT, tyramine and DMPP were inhibited by propranolol and practolol and the pA2 values obtained were similar to those obtained with noradrenaline as the agonist. 3 Responses to 5-HT, tyramine and DMPP were greatly reduced on hearts from rabbits pretreated with 6-hydroxydopamine. Such hearts had less than 7% of their normal catecholamine concentration and no fluorescence characteristic of noradrenaline in the cardiac sympathetic nerves could be demonstrated. 4 Rapid, reversible and selective tachyphylaxis to 5-HT was demonstrated during perfusion with 5-HT. In hearts desensitized to DMPP by perfusion with DMPP, responses to 5-HT were also reduced. 5 Perfusion of hearts with colchicine inhibited stimulant responses to 5-HT and DMPP but had little effect on responses to noradrenaline or tyramine. 6 Desmethylimipramine enhanced cardiac stimulant responses to noradrenaline and to a lesser extent, those to 5-HT and DMPP. Responses to tyramine were consistently inhibited by desmethylimipramine. 7 Tetrodotoxin abolished responses of the heart to electrical nerve stimulation but left responses to noradrenaline, 5-HT and DMPP unaffected. 8 5-HT, tyramine and DMPP evoked 3H-release from hearts whose neuronal noradrenaline stores had been labelled by perfusion with [3H]-(-)-noradrenaline. The pattern of release evoked by 5-HT was similar to that of DMPP but differed from that of tyramine. 9 Reducing the calcium concentration in the Tyrode solution from 3.6 to 0.2 mEq/1 did not affect 3H-overflow after tyramine but greatly inhibited that evoked by 5-HT and DMPP. 10 The results confirm that the stimulatn effects of 5-HT on the rabbit isolated heart are the result of noradrenaline release. They further suggest that the site of the release is the terminal sympathetic nerve network. The mechanism of release shows more similarities to that of DMPP (calcium-dependent depolarization and exocytosis) than to that of tyramine (neuronal uptake and stoichiometric displacement).
采用Langendorff技术灌注的兔离体心脏用于研究5-羟色胺（5-HT）的间接拟交感神经效应。将其与去甲肾上腺素以及两种作用机制完全不同的间接拟交感神经药酪胺和二甲基苯基哌嗪鎓（DMPP）进行了比较。
普萘洛尔和普拉洛尔抑制了5-HT、酪胺和DMPP的心脏兴奋作用，得到的pA2值与以去甲肾上腺素为激动剂时获得的值相似。
用6-羟基多巴胺预处理的兔心脏对5-HT、酪胺和DMPP的反应大大降低。此类心脏的儿茶酚胺浓度低于正常浓度的7%，且心脏交感神经中未显示出去甲肾上腺素特有的荧光。
在5-HT灌注期间证明了对5-HT的快速、可逆和选择性快速耐受性。在用DMPP灌注使心脏对DMPP脱敏后，对5-HT的反应也降低。
用秋水仙碱灌注心脏抑制了对5-HT和DMPP的兴奋反应，但对去甲肾上腺素或酪胺的反应影响很小。
去甲丙咪嗪增强了心脏对去甲肾上腺素的兴奋反应，对5-HT和DMPP的反应增强程度较小。去甲丙咪嗪始终抑制对酪胺的反应。
河豚毒素消除了心脏对电刺激神经的反应，但对去甲肾上腺素、5-HT和DMPP的反应无影响。
5-HT、酪胺和DMPP从经[3H]-（-）-去甲肾上腺素灌注标记了神经元去甲肾上腺素储备的心脏中诱发3H释放。5-HT诱发的释放模式与DMPP相似，但与酪胺不同。
将台氏液中的钙浓度从3.6 mEq/1降至0.2 mEq/1不影响酪胺后的3H溢出，但大大抑制了5-HT和DMPP诱发的3H溢出。
结果证实5-HT对兔离体心脏的刺激作用是去甲肾上腺素释放的结果。它们进一步表明释放部位是终末交感神经网络。释放机制与DMPP（钙依赖性去极化和胞吐作用）的机制比与酪胺（神经元摄取和化学计量置换）的机制更相似。
