Ternaux J P, Boireau A, Bourgoin S, Hamon M, Hery F, Glowinski J
Brain Res. 1976 Jan 23;101(3):533-48. doi: 10.1016/0006-8993(76)90476-5.
The in vivo release of 5-HT was examined in the rat brain. For this purpose, the left lateral ventricle was perfused at a constant rate with an artificial CSF for several hours in animals anaesthetized with halothane. 5-HT was estimated in serial 1-h collected fractions. The amine was first isolated by adsorption on a Sephadex G-10 column and then assayed using the radioenzymatic method of Saavedra et al.37, slightly modified to improve its sensitivity. The quantity of 5-HT released spontaneously during the first hour fraction was 296 pg, it was lower (99 pg/h) in the following fractions. 5-HT released into the CSF may in great part originate from serotoninergic terminals localized in structures surrounding the ventricle. This was suggested by experiments in which exogenous [3H]5-HT or [3H]tryptophan were perfused through the lateral ventricle during a few hours. [3H]5-HT taken up or synthetized was mainly localized in structures surrounding the ventricular space. The acute injection of 5-hydroxytryptophan (100 mg/kg) induced an immediate important and long lasting increase of 5-HT release. In contrast the acute injection of tryptophan (100 mg/kg) led to a transient and moderate elevation of 5-HT release which was only detected during the second hour of perfusion. Curiously a similar pattern of transmitter release was observed following the constant intravenous infusion of the amino acid (70 mg/kg/h) except that the increase in 5-HT release was much more pronounced during the second hour than after the acute injection. Parallel experiments were made to determine the time course of the changes of free and total tryptophan levels in plasma and of those of tryptophan, 5-HT, and 5-hydroxyindoleacetic-acid (5-HIAA) in brain tissues, induced by the acute and long term administrations of tryptophan. Moreover the rate of 5-HT synthesis was estimated using the monoamine oxidase inhibition method 2 and 5 h after both tryptophan treatments in halothane anaesthetized rats. 5-HT levels and the synthesis rate of the transmitter were increased at 2 h (when both tryptophan treatments stimulated 5-HT release). Despite the presence of high tryptophan levels in plasma and tissues and of high 5-HT and 5-HIAA levels in tissues, the synthesis rate of 5-HT (as the 5-HT release) was similar to that of controls 5 h after the onset of tryptophan infusion. These results suggest that some relationships occurred between the changes in 5-HT SYNTHESIs and release after the first hour of perfusion. The absence of effects of tryptophan treatments on 5-HT release during the first hour of perfusion are also discussed.
在大鼠脑中检测了5-羟色胺（5-HT）的体内释放情况。为此，在用氟烷麻醉的动物中，以恒定速率向左侧脑室灌注人工脑脊液数小时。在连续1小时收集的馏分中对5-HT进行评估。首先通过吸附在葡聚糖G-10柱上分离该胺，然后使用Saavedra等人的放射酶法进行测定，并稍作修改以提高其灵敏度。在第一个小时馏分中自发释放的5-HT量为296皮克，在随后的馏分中较低（99皮克/小时）。释放到脑脊液中的5-HT可能在很大程度上源自位于脑室周围结构中的5-羟色胺能终末。这是通过以下实验表明的，即外源[3H]5-HT或[3H]色氨酸在数小时内通过侧脑室灌注。摄取或合成的[3H]5-HT主要位于脑室空间周围的结构中。急性注射5-羟色氨酸（100毫克/千克）导致5-HT释放立即显著且持久增加。相比之下，急性注射色氨酸（100毫克/千克）导致5-HT释放短暂且适度升高，仅在灌注的第二个小时检测到。奇怪的是，在持续静脉输注氨基酸（70毫克/千克/小时）后观察到类似的递质释放模式，只是在第二个小时5-HT释放的增加比急性注射后更明显。进行了平行实验以确定色氨酸急性和长期给药诱导的血浆中游离和总色氨酸水平以及脑组织中色氨酸、5-HT和5-羟吲哚乙酸（5-HIAA）水平变化的时间进程。此外，在氟烷麻醉的大鼠中，在色氨酸两种处理后2小时和5小时使用单胺氧化酶抑制法估计5-HT的合成速率。在2小时时（当两种色氨酸处理均刺激5-HT释放时）5-HT水平和递质的合成速率增加。尽管血浆和组织中存在高色氨酸水平以及组织中存在高5-HT和5-HIAA水平，但在色氨酸输注开始5小时后5-HT的合成速率（如5-HT释放）与对照相似。这些结果表明在灌注的第一个小时后5-HT合成和释放的变化之间存在一些关系。还讨论了色氨酸处理在灌注的第一个小时对5-HT释放无影响的情况。
