Branco D, Osswald W
Laboratório de Farmacologia, Faculdade de Medicina, Porto, Portugal.
Fundam Clin Pharmacol. 1988;2(6):477-91. doi: 10.1111/j.1472-8206.1988.tb00649.x.
The spontaneous efflux of endogenous noradrenaline, dopamine, dihydroxyphenylglycol (DOPEG) from adrenergic nerve endings of 2 canine blood vessels (the mesenteric artery and the saphenous vein) were studied during 8 successive incubation periods of 15 min each. Extraneuronal uptake and O-methylation were minimized by the presence of adequate concentrations of tropolone and hydrocortisone. Both vessels had an efflux characterized by a decline in the 3 catechols, which was most marked for noradrenaline; the mesenteric artery lost larger amounts than the saphenous vein. Ouabain caused a large increase in the efflux of noradrenaline and dopamine and a reduction of DOPEG efflux. Cocaine had only a modest effect, more evident in the case of the mesenteric artery, increasing noradrenaline and reducing DOPEG effluxes. The combination of ouabain and cocaine had no additive effects, and the effects of ouabain were even reduced (on some parameters) by cocaine. Accordingly, the noradrenaline:DOPEG ratio was markedly increased by ouabain, but not by cocaine; cocaine significantly reduced the effects of ouabain. The ratio dopamine:noradrenaline was decreased by cocaine and by ouabain. Comparison of tissue content and efflux allowed us to conclude that apparently no significant de novo synthesis of noradrenaline occurred during the incubation period. We conclude that a fast and early component of spontaneous efflux is due to loss from the neurons and that its greater magnitude in the mesenteric artery may be due to differences in neuronal [Na+] and/or to differences in neuronal membrane adenosine triphosphatase activity. The results also suggest that neuronal reuptake plays only a minor role in the handling of spontaneously released noradrenaline.
在连续8个15分钟的孵育期内，研究了2条犬类血管（肠系膜动脉和隐静脉）肾上腺素能神经末梢内源性去甲肾上腺素、多巴胺、二羟苯乙二醇（DOPEG）的自发外流情况。通过加入适当浓度的托酚酮和氢化可的松，使神经元外摄取和O - 甲基化作用降至最低。两条血管的外流均表现为3种儿茶酚胺含量下降，其中去甲肾上腺素下降最为明显；肠系膜动脉损失的量比隐静脉更多。哇巴因使去甲肾上腺素和多巴胺的外流大幅增加，DOPEG外流减少。可卡因的作用较小，在肠系膜动脉中更为明显，可增加去甲肾上腺素外流并减少DOPEG外流。哇巴因和可卡因联合使用无相加作用，且可卡因甚至会降低哇巴因的某些作用（某些参数上）。因此，哇巴因可显著提高去甲肾上腺素与DOPEG的比值，但可卡因无此作用；可卡因可显著降低哇巴因的作用。可卡因和哇巴因均可降低多巴胺与去甲肾上腺素的比值。通过比较组织含量和外流情况，我们得出结论，在孵育期内，去甲肾上腺素显然没有明显的从头合成。我们得出结论，自发外流的快速早期成分是由于神经元释放造成的，肠系膜动脉中该成分量更大可能是由于神经元[Na⁺]的差异和/或神经元膜三磷酸腺苷酶活性的差异。结果还表明，神经元再摄取在处理自发释放的去甲肾上腺素过程中仅起次要作用。
