MECHANISM OF THE INDIRECT SYMPATHOMIMETIC EFFECT OF 5‐HYDROXYTRYPTAMINE ON THE ISOLATED HEART OF THE RABBIT
MECHANISM OF THE INDIRECT SYMPATHOMIMETIC EFFECT OF 5‐HYDROXYTRYPTAMINE ON THE ISOLATED HEART OF THE RABBIT
复制标题
5-羟色胺对家兔离体心脏间接拟交感作用的机制
DOI：
10.1111/j.1476-5381.1976.tb07661.x
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发表时间：
1976
影响因子：
7.3
通讯作者：
G. Mwaluko
中科院分区：
文献类型：
--
作者：
J. Fozard;G. Mwaluko
1采用Langendorff灌流技术，观察5-羟色胺（5-HT）对离体兔心脏的间接拟交感神经作用。与去甲肾上腺素和两个间接作用的拟交感神经药物具有完全不同的作用机制，酪胺和二甲基苯基哌嗪（DMPP）进行了比较。2普萘洛尔和普萘洛尔均能抑制5-HT、酪胺和DMPP的强心作用，其pA 2值与去甲肾上腺素类似。3在用6-羟基多巴胺预处理的家兔心脏上，对5-HT、酪胺和DMPP的反应大大降低。这种心脏的儿茶酚胺浓度低于正常值的7%，心脏交感神经中无去甲肾上腺素的荧光特征。4在5-HT灌注过程中，显示了对5-HT的快速、可逆和选择性快速耐受。在通过灌注DMPP对DMPP脱敏的心脏中，对5-HT的反应也降低。5.心脏灌注秋水仙碱可抑制对5-HT和DMPP的兴奋性反应，但对去甲肾上腺素或酪胺的反应几乎没有影响。6去甲丙咪嗪增强了对去甲肾上腺素的心脏刺激反应，并在较小程度上增强了对5-HT和DMPP的心脏刺激反应。对酪胺的反应始终受到去甲丙咪嗪的抑制。7河豚毒素消除了心脏对电神经刺激的反应，但对去甲肾上腺素、5-HT和DMPP的反应不受影响。8 5-HT、酪胺和DMPP诱发了心脏的3 H-释放，心脏的神经元去甲肾上腺素储存已通过灌注[3 H]-（-）-去甲肾上腺素标记。5-HT诱发的释放模式与DMPP相似，但与酪胺不同。9将台氏液中的钙浓度从3.6 mEq/l降低至0.2 mEq/l并不影响酪胺后的3 H-溢出，但极大地抑制了5-HT和DMPP诱发的3 H-溢出。结果证实，5-HT对家兔离体心脏的兴奋作用是去甲肾上腺素释放的结果。他们进一步表明，释放的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）的相似性大于酪胺（神经元摄取和化学计量置换）。
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 stimulant 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).