Grohmann M, Trendelenburg U
Institut für Pharmakologie und Toxikologie der Universität, Würzburg, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Feb;337(2):159-63. doi: 10.1007/BF00169243.
The handling of five amines by the extraneuronal deaminating system was studied in perfused hearts of rats (pretreated with reserpine; COMT and neuronal uptake inhibited). Hearts were perfused with 50 nmol/l 3H-noradrenaline for 30 min, in the presence of increasing concentrations of unlabelled (-)-adrenaline, (-)-noradrenaline, dopamine, tyramine and 5-HT. IC50's were determined as those concentrations of unlabelled amines which halved the steady-state rate of deamination of 3H-noradrenaline. After correction for changes in the tissue/medium ratio for 3H-noradrenaline, "half-saturating outside concentrations" were obtained. They increased in the order (-)-adrenaline (15 mumol/l) - tyramine - dopamine - noradrenaline - 5-HT (53 mumol/l). The Vmax for extraneuronal deamination was determined for 3H-(-)-adrenaline, 3H-(-)-noradrenaline and 3H-dopamine, as well as (by HPLC and electrochemical detection) for tyramine and 5-HT. It was low for (-)-adrenaline, intermediate for (-)-noradrenaline, dopamine and 5-HT, high for tyramine. For the three catecholamines the half-saturating outside concentrations of the extraneuronal deaminating system clearly exceeded those for the extraneuronal O-methylating system of the same organ (see Grohmann and Trendelenburg 1985), although the two enzymes appear to co-exist in the same cells, so that the same transport system is involved.
在大鼠(用利血平预处理;儿茶酚-O-甲基转移酶和神经元摄取被抑制)的灌注心脏中研究了细胞外脱氨基系统对五种胺的处理。心脏在存在浓度不断增加的未标记的(-)-肾上腺素、(-)-去甲肾上腺素、多巴胺、酪胺和5-羟色胺的情况下,用50 nmol/l的3H-去甲肾上腺素灌注30分钟。半数抑制浓度(IC50)被确定为那些使3H-去甲肾上腺素脱氨基的稳态速率减半的未标记胺的浓度。在对3H-去甲肾上腺素的组织/培养基比率变化进行校正后,获得了“半饱和外部浓度”。它们按以下顺序增加:(-)-肾上腺素(15 μmol/l)-酪胺-多巴胺-去甲肾上腺素-5-羟色胺(53 μmol/l)。测定了细胞外脱氨基对3H-(-)-肾上腺素、3H-(-)-去甲肾上腺素和3H-多巴胺的最大反应速度(Vmax),以及(通过高效液相色谱和电化学检测)对酪胺和5-羟色胺的Vmax。(-)-肾上腺素的Vmax较低,(-)-去甲肾上腺素、多巴胺和5-羟色胺的Vmax中等,酪胺的Vmax较高。对于这三种儿茶酚胺,细胞外脱氨基系统的半饱和外部浓度明显超过同一器官的细胞外O-甲基化系统的半饱和外部浓度(见Grohmann和Trendelenburg,1985),尽管这两种酶似乎共存于相同的细胞中,因此涉及相同的转运系统。