Jin S
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Neuropharmacology. 1997 Nov-Dec;36(11-12):1503-10. doi: 10.1016/s0028-3908(97)00166-4.
Rat striatal slices, preincubated with [3H]dopamine (DA) and [14C]choline, were superfused continuously. Detection of radioactivity was used to monitor the release of the neurotransmitters DA and acetylcholine (ACh). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX) caused a concentration-dependent decrease in 100 microM alpha-amino-3-hydroxy-5-methylisoxazol-4-propionate (AMPA)-, 100 microM kainate- or 100 mM glutamate-induced release of DA and ACh. The IC50 of NBQX is 3-fold higher (for ACh release) and is 2-fold lower (for DA release) than that of CNQX. This is in agreement with the IC50 ratio of NBQX and CNQX on kainate- and AMPA-receptor binding. These two antagonists, at doses that produce an equivalent blockade of kainate-receptor binding (5 microM for NBQX and 1.56 microM for CNQX), caused an approximately equal decrease in ACh- but not DA-release induced by 100 microM kainate or AMPA. At doses that produce an equivalent blockade of AMPA-receptor binding (5 microM for NBQX and 10 microM for CNQX), they caused an approximately equal decrease in DA but not ACh release induced by 100 microM AMPA or kainate. Moreover, concanavalin A (0.3 and 0.5 mg/ml), which selectively potentiates kainate-receptor responses, markedly enhanced 100 microM kainate-induced release of ACh but not DA. Cyclothiazide (10 microM), which selectively potentiates AMPA-receptor responses, significantly increased 100 microM AMPA- or kainate-induced release of DA but not ACh. In summary, these results indicate that AMPA-and kainate-receptor activation, respectively, are predominantly involved in excitatory amino acid (EAA)-induced DA and ACh release in the striatum.
用[3H]多巴胺（DA）和[14C]胆碱预孵育的大鼠纹状体切片，持续进行灌流。通过检测放射性来监测神经递质DA和乙酰胆碱（ACh）的释放。6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）和2,3-二羟基-6-硝基-7-氨磺酰基苯并[f]喹喔啉（NBQX）使100微摩尔α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）、100微摩尔海人藻酸或100毫摩尔谷氨酸诱导的DA和ACh释放呈浓度依赖性降低。NBQX的半数抑制浓度（IC50）比CNQX高3倍（对于ACh释放）且低2倍（对于DA释放）。这与NBQX和CNQX对海人藻酸受体和AMPA受体结合的IC50比值一致。这两种拮抗剂在产生等效海人藻酸受体结合阻断作用的剂量下（NBQX为5微摩尔，CNQX为1.56微摩尔），使100微摩尔海人藻酸或AMPA诱导的ACh释放减少程度大致相同，但对DA释放无影响。在产生等效AMPA受体结合阻断作用的剂量下（NBQX为5微摩尔，CNQX为10微摩尔），它们使100微摩尔AMPA或海人藻酸诱导的DA释放减少程度大致相同，但对ACh释放无影响。此外，刀豆球蛋白A（0.3和0.5毫克/毫升）可选择性增强海人藻酸受体反应，显著增强100微摩尔海人藻酸诱导的ACh释放，但对DA释放无影响。环噻嗪（10微摩尔）可选择性增强AMPA受体反应，显著增加100微摩尔AMPA或海人藻酸诱导的DA释放，但对ACh释放无影响。总之，这些结果表明，AMPA受体和海人藻酸受体的激活分别主要参与纹状体中兴奋性氨基酸（EAA）诱导的DA和ACh释放。
