Numazawa R
Department of Anesthesiology, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1994 Jul;69(4):927-39.
The purpose of the present study is to confirm the functional regulation of alpha 2-adrenoceptor on the release of serotonin (5-HT) from the rat hippocampus in vivo. Under several pharmacological conditions, extracellular levels of 5-HT were estimated by assaying its concentrations in the perfusion fluid through the use of high-performance liquid chromatography with electrochemical detection. Extracellular 5-HT in the hippocampus was reduced by tetrodotoxin, 10 microM co-perfusion and was increased by perfusion with a selective 5-HT reuptake inhibitor, fluoxetine, 10 microM. Addition of potassium (K+; 120 mM) to the perfusion fluid evoked an approximately 3-fold increase in 5-HT release, and a calcium free medium completely prevented this K(+)-evoked 5-HT release. Potassium-evoked 5-HT release from the hippocampus of freely moving rats was significantly and concentration-dependently inhibited when alpha 2-adrenoceptor agonist, UK14,304, 0.1 microM to 10 microM was added to the perfusion solution, while the output of a 5-HT major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), remained unchanged. This action of UK14,304 was prevented by pretreatment with idazoxan, 5 mg/kg, i. p., an alpha 2-adrenoceptor antagonist. In rats that were catecholaminergically denervated with 6-hydroxydopamine, UK14,304, 10 microM also inhibited the potassium-evoked 5-HT release, but had no effect on the 5-HIAA output. The UK14,304-induced inhibition of 5-HT release was prevented by pretreatment with pertussis toxin (PTX). These findings suggest that 5-HT release is functionally modulated via alpha 2-adrenoceptors located on the serotonergic nerve terminals in the rat hippocampus. They also indicate the possibility that the inhibition of 5-HT release via alpha 2-adrenoceptors is linked to G-proteins which are substrates of PTX.
本研究的目的是在体内证实α2 -肾上腺素能受体对大鼠海马中5 -羟色胺（5 - HT）释放的功能调节。在几种药理学条件下，通过使用高效液相色谱 - 电化学检测法测定灌注液中5 - HT的浓度来估计其细胞外水平。海马中的细胞外5 - HT被河豚毒素、10μM共灌注降低，并被10μM选择性5 - HT再摄取抑制剂氟西汀灌注增加。向灌注液中添加钾离子（K +；120 mM）可使5 - HT释放增加约3倍，而无钙培养基可完全阻止这种钾离子诱发的5 - HT释放。当向灌注溶液中添加0.1μM至10μM的α2 -肾上腺素能受体激动剂UK14,304时，自由活动大鼠海马中钾离子诱发的5 - HT释放受到显著且浓度依赖性的抑制，而5 - HT主要代谢产物5 -羟吲哚乙酸（5 - HIAA）的产量保持不变。UK14,304的这种作用可被α2 -肾上腺素能受体拮抗剂咪唑克生（5 mg/kg，腹腔注射）预处理所阻断。在用6 -羟基多巴胺进行儿茶酚胺能去神经支配的大鼠中，10μM的UK14,304也抑制钾离子诱发的5 - HT释放，但对5 - HIAA产量无影响。UK14,304诱导的5 - HT释放抑制可被百日咳毒素（PTX）预处理所阻断。这些发现表明，5 - HT释放通过位于大鼠海马中5 -羟色胺能神经末梢上的α2 -肾上腺素能受体进行功能调节。它们还表明，通过α2 -肾上腺素能受体抑制5 - HT释放可能与作为PTX底物的G蛋白有关。
