Russ H, Schömig E, Trendelenburg U
Institut für Pharmakologie und Toxikologie, Universität Würzburg, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1991 Sep;344(3):286-96. doi: 10.1007/BF00183002.
In the rat vas deferens (preloaded with 3H-noradrenaline, catechol-O-methyl transferase inhibited, calcium-free solution) ouabain, glucose deprivation or the combination of hypoxia plus presence of lactate were found to induce a carrier-mediated (desipramine-sensitive) outward transport of the 3H-amine. Glucose deprivation additionally increased the efflux of deaminated 3H-metabolites, as a consequence of an increased net leakage of vesicular 3H-noradrenaline; moreover, 3H-dihydroxymandelic acid then became the predominant neuronal metabolite. The simultaneous lack of oxygen and glucose resulted in a very pronounced release of the 3H-amine. Moreover, during spontaneous efflux more outward transport of 3H-noradrenaline was observed in the absence than in the presence of extracellular calcium. In rat atria (under the same experimental conditions) the contribution by carrier-mediated outward transport to the spontaneous efflux of tritium exceeded that in vasa deferentia. Moreover, the efflux of lactate (as an index of hypoxia of the tissue) exceeded that observed in vasa deferentia, under aerobic and anaerobic conditions. It is proposed that the greater contribution by outward transport of 3H-noradrenaline to spontaneous efflux in atria than in vasa deferentia does not reflect any basic difference between the varicosities in two different organs. It is likely that the less heterogeneous distribution of the 3H-amine in atria than in vasa deferentia is responsible for storage of the exogenous amine in atrial varicosities that are subject to some hypoxia, to an increased extracellular lactate level and to perhaps a minor degree of glucose deficiency; these factors may well be responsible for the difference with regard to outward transport of 3H-noradrenaline during spontaneous efflux. Thus, in addition to the heterogeneity of the distribution of 3H-noradrenaline, an additional heterogeneity with regard to the energy supply must be expected for incubated organs.
在大鼠输精管(预先装载3H - 去甲肾上腺素,儿茶酚 - O - 甲基转移酶被抑制,无钙溶液)中,发现哇巴因、葡萄糖剥夺或缺氧加乳酸存在的组合可诱导载体介导的(地昔帕明敏感的)3H - 胺外向转运。葡萄糖剥夺还增加了脱氨基3H - 代谢物的流出,这是由于囊泡3H - 去甲肾上腺素净泄漏增加所致;此外,3H - 二羟扁桃酸随后成为主要的神经元代谢物。同时缺乏氧气和葡萄糖导致3H - 胺的非常明显的释放。此外,在自发流出过程中,在无细胞外钙的情况下比有细胞外钙时观察到更多的3H - 去甲肾上腺素外向转运。在大鼠心房(在相同实验条件下),载体介导的外向转运对氚自发流出的贡献超过输精管。此外,在有氧和无氧条件下,乳酸的流出(作为组织缺氧的指标)超过在输精管中观察到的流出。有人提出,3H - 去甲肾上腺素外向转运对心房自发流出的贡献大于输精管,这并不反映两个不同器官曲张体之间的任何基本差异。很可能是心房中3H - 胺的分布比输精管中更不均匀,导致外源性胺储存在一些缺氧、细胞外乳酸水平升高以及可能轻度葡萄糖缺乏的心房曲张体中;这些因素很可能是自发流出过程中3H - 去甲肾上腺素外向转运差异的原因。因此,除了3H - 去甲肾上腺素分布的不均匀性外,对于孵育的器官,还必须预期能量供应方面的额外不均匀性。