The Effects of Benzodiazepines on Urotensin II-Stimulated Norepinephrine Release from Rat Cerebrocortical Slices
The Effects of Benzodiazepines on Urotensin II-Stimulated Norepinephrine Release from Rat Cerebrocortical Slices
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DOI：
10.1213/ane.0b013e3181981faa
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发表时间：
2009-04-01
影响因子：
5.7
通讯作者：
Hirota, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Kawaguchi, Yoko;Ono, Tomoko;Hirota, Kazuyoshi
背景技术背景：尾加压素II（UII）及其受体（UT）与情绪障碍如应激和焦虑有关，这可能至少部分是由于大脑皮层释放的去甲肾上腺素增加所致。苯二氮卓类药物已被广泛用作催眠药和抗焦虑药，可减少肾上腺皮质去甲肾上腺素的释放。我们假设苯二氮卓类药物和大脑皮层UII系统之间存在某种相互作用。方法：在本研究中，我们检测了苯二氮卓类药物对大鼠脑皮层切片中UII增加的去甲肾上腺素释放和表达大鼠UT受体的HEK293细胞内Ca 2+浓度（[Ca 2 +]i）的影响结果：咪达唑仑、地西泮和氟硝西泮浓度依赖性地抑制UII诱导的去甲肾上腺素释放，但不影响[Ca2+]i。咪达唑仑抑制UII诱发的去甲肾上腺素释放的IC_（50）（0.32 μ M，P < 0.01）显著低于地西泮（187 μ M）或氟硝西泮（40 μ M）。咪达唑仑对UII诱发的去甲肾上腺素释放的抑制作用被苯二氮卓类药物受体拮抗剂氟马西尼显著减弱。结论：本研究表明，咪达唑仑在临床相关浓度下，显著抑制UII诱发的去甲肾上腺素释放。这种抑制作用可能部分通过中枢苯二氮卓受体介导。
BACKGROUND: Urotensin II (UII) and its receptor (UT) are implicated in mood disorders, such as stress and anxiety, and this may result, at least in part, from increased norepinephrine release from the cerebral cortex. Benzodiazepines have been widely used as hypnotics and anxiolytics, producing a decrease in cerebrocortical norepinephrine release. We hypothesized that there was some interaction between benzodiazepines and the UII system in the cerebral cortex.METHODS: In the present study, we have examined the effects of benzodiazepines on UII-increased norepinephrine release from rat cerebrocortical slices and intracellular Ca2+ concentrations ([Ca2+]i) in HEK293 cells expressing rat UT receptor (HEK293-rUT cells).RESULTS: Midazolam, diazepam and flunitrazepam concentration-dependently inhibited UII-evoked norepinephrine release but did not affect [Ca2+]i. The IC50 of midazolam for inhibition of UII-evoked norepinephrine release (0.32 mu M, P < 0.01) was significantly lower than that of diazepam (187 mu M) or flunitrazepam (40 mu M). The inhibitory effects of midazolam on UII-evoked norepinephrine release were significantly attenuated by flumazenil, a benzodiazepine site antagonist.CONCLUSION: The present study suggests that midazolam, at clinically relevant concentration, significantly inhibited UII-evoked norepinephrine release. This inhibitory effect may be partially mediated via central benzodiazepine receptors.