Badoer E, Würth H, Türck D, Qadri F, Itoi K, Dominiak P, Unger T
Department of Pharmacology, University of Heidelberg, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):54-9. doi: 10.1007/BF00165126.
The novel technique of microdialysis has been used to examine the basal and K+-induced release of catecholamines and metabolites from the anterior hypothalamus of the urethane-anaesthetized rat in vivo. A high pressure liquid chromatographic assay was developed to simultaneously measure endogenous noradrenaline, dopamine and their intraneuronal metabolites 3,4-dihydroxyphenylglycol (DOPEG) and 3,4-dihydroxyphenylacetic acid (DOPAC) respectively, in each 60 microliters dialysate sample. The effect of replacing Ca2+ in the perfusion fluid with a low concentration of Cd2+, which blocks Ca2+ effects, was also studied. Increasing the K+ concentration in the perfusion fluid elicited a concentration-dependent increase in noradrenaline and dopamine release. In contrast, there were marked reductions in DOPEG and DOPAC which were not concentration-dependent. In the Ca2+-depleted conditions, the K+-induced increase in amine release was significantly attenuated, but the reductions in the metabolites were not affected. We suggest that the mechanisms contributing to the observed reductions in the metabolites may be inhibition of neuronal reuptake, an increase in neuronal efflux, an enhancement of vesicular uptake and a decrease in vesicular efflux.
微透析这项新技术已被用于检测在体的经氨基甲酸乙酯麻醉的大鼠下丘脑前部中儿茶酚胺及其代谢产物的基础释放量以及钾离子诱导的释放量。已开发出一种高压液相色谱分析法,用于同时测量每60微升透析液样本中内源性去甲肾上腺素、多巴胺及其神经元内代谢产物3,4-二羟基苯乙二醇(DOPEG)和3,4-二羟基苯乙酸(DOPAC)的含量。还研究了用低浓度的镉离子(Cd2+)替代灌注液中的钙离子(Ca2+)(这会阻断钙离子的作用)所产生的影响。增加灌注液中钾离子的浓度会引起去甲肾上腺素和多巴胺释放量呈浓度依赖性增加。相反,DOPEG和DOPAC的释放量则显著减少,且不具有浓度依赖性。在钙离子缺失的情况下,钾离子诱导的胺类释放增加显著减弱,但代谢产物的减少不受影响。我们认为,导致观察到的代谢产物减少的机制可能是神经元再摄取的抑制、神经元外流的增加、囊泡摄取的增强以及囊泡外流的减少。