Numazawa R, Yoshioka M, Matsumoto M, Togashi H, Kemmotsu O, Saito H
Department of Anesthesiology, Hokkaido University School of Medicine, Sapporo, Japan.
Neurosci Lett. 1995 Jun 16;192(3):161-4. doi: 10.1016/0304-3940(95)11635-a.
The purpose of the present study was to confirm the functional regulation by alpha 2-adrenoceptors of 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 perfusate by high performance liquid chromatography with electrochemical detection. Extracellular 5-HT in the hippocampus was reduced by tetrodotoxin (10 microM) co-perfusion, but increased by perfusion of a selective 5-HT re-uptake inhibitor, fluoxetine (10 microM). Addition of potassium (K+, 120 mM) to the perfusion fluid evoked an approximately 3-fold increase in 5-HT release. When the alpha 2-adrenoceptor agonist UK14,304 (0.1-10 microM) was added to the perfusion solution, the K(+)-evoked 5-HT release was significantly inhibited in a concentration-dependent manner. This inhibitory action of UK14,304 was reversed by pretreatment with an alpha 2-adrenoceptor antagonist, idazoxan (5 mg/kg, i.p.). In rats which were catecholaminergically denervated with 6-hydroxydopamine, UK14,304 (10 microM) still inhibited the K(+)-evoked 5-HT release. Treatment with pertussis toxin (PTX) did not alter the K(+)-evoked release of 5-HT but abolished the inhibitory effect of UK14,304. These findings suggest that 5-HT release is functionally modulated via alpha 2-adrenoceptors located on the serotonergic nerve terminals in the rat hippocampus and furthermore, the possibility that the inhibitory of 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大鼠海马中5-羟色胺（5-HT）释放的α2-肾上腺素能受体功能调节。在几种药理学条件下，通过高效液相色谱电化学检测法测定灌流液中5-HT的浓度来估计其细胞外水平。海马中的细胞外5-HT通过与河豚毒素（10微摩尔）共同灌流而降低，但通过灌注选择性5-HT再摄取抑制剂氟西汀（10微摩尔）而增加。向灌流液中添加钾离子（K+，120毫摩尔）可使5-HT释放增加约3倍。当向灌流液中添加α2-肾上腺素能受体激动剂UK14,304（0.1 - 10微摩尔）时，钾离子诱发的5-HT释放以浓度依赖的方式受到显著抑制。UK14,304的这种抑制作用可被α2-肾上腺素能受体拮抗剂咪唑克生（5毫克/千克，腹腔注射）预处理所逆转。在用6-羟基多巴胺进行儿茶酚胺能去神经支配的大鼠中，UK14,304（10微摩尔）仍能抑制钾离子诱发的5-HT释放。百日咳毒素（PTX）处理并未改变钾离子诱发的5-HT释放，但消除了UK14,304的抑制作用。这些发现表明，5-HT释放是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的，此外，α2-肾上腺素能受体的抑制作用可能与作为PTX底物的G蛋白有关。
