Urotensin II evokes neurotransmitter release from rat cerebrocortical slices
Urotensin II evokes neurotransmitter release from rat cerebrocortical slices
复制标题
DOI：
10.1016/j.neulet.2008.05.096
复制
发表时间：
2008-08
影响因子：
2.5
通讯作者：
Tomoko Ono;Yoko Kawaguchi;M. Kudo;T. Kushikata;E. Hashiba;H. Yoshida;T. Kudo;Kenichi Furukawa;S. Douglas;R. Guerrini;G. Calo’;K. Hirota
中科院分区：
文献类型：
--
作者：
Tomoko Ono;Yoko Kawaguchi;M. Kudo;T. Kushikata;E. Hashiba;H. Yoshida;T. Kudo;Kenichi Furukawa;S. Douglas;R. Guerrini;G. Calo’;K. Hirota
据报道，尾加压素 II (UII) 通过激活脑干胆碱能神经元来调节快速眼动 (REM) 睡眠，而快速眼动睡眠则由蓝斑 (LC)——脑皮质去甲肾上腺素能神经元调节。我们假设 UII 可能激活 LC-大脑皮质去甲肾上腺素能神经元。为了验证这一假设，我们研究了 UII 对大鼠大脑皮质切片去甲肾上腺素释放的影响。此外，还评估了假定的 UT 受体拮抗剂 [Pen5、DTrp7、Dab8]UII(4–11) (UFP-803) 的作用。我们将其与其他促进觉醒的神经递质（如多巴胺、谷氨酸、血清素和组胺）进行了比较。我们还研究了UII和UFP-803对稳定表达大鼠UT受体的HEK293细胞（HEK293-rUT细胞）细胞内Ca2+（[Ca2+]i）的影响。 UII 产生时间（10nM 刺激后约 10 分钟达到峰值）和浓度依赖性去甲肾上腺素释放增加，pEC50 和 Emax（基础百分比）值分别为 8.78±0.17 (1.65nM) 和 138±2%。 UII 还引起多巴胺、血清素和组胺释放，具有相似的 pEC50 值。 UII 增加了谷氨酸的释放，但仅在高浓度 (<100nM) 下，并且未能达到饱和。 UII 以浓度依赖性方式显着增加 HEK293-rUT 细胞中的 [Ca2+]i，pEC50 为 8.26±0.24。 UT 拮抗剂 UFP-803 逆转了 HEK293-rUT 细胞中 UII 增加的脑皮质切片 (pKB=8.98) 和 [Ca2+]i(pKB=8.87) 的去甲肾上腺素释放。总的来说，这些数据表明 UII 通过 UT 受体激活引起去甲肾上腺素的释放，并对其他促进觉醒的神经递质产生类似的作用：UII 的这些神经化学作用可能对于控制睡眠-觉醒周期很重要。
Urotensin II (UII) has been reported to modulate rapid eye movement (REM) sleep via activation of brainstem cholinergic neurons and REM sleep is regulated by locus coerleus (LC)–cerebrocortical noradrenergic neurons. We hypothesized that UII may activate LC–cerebrocortical noradrenergic neurons. To test this hypothesis, we have examined the effects of UII on norepinephrine release from rat cerebrocortical slices. In addition, the effect of the putative UT receptor antagonist [Pen5, DTrp7, Dab8]UII(4–11) (UFP-803) was assessed. We have compared this with other wakefulness-promoting neurotransmitters such as dopamine, glutamate, serotonin and histamine. We also studied the effects of UII and UFP-803 on intracellular Ca2+([Ca2+]i) in HEK293 cells stably expressing rat UT receptor (HEK293-rUT cells). UII produced a time- (peaking at ∼10min following stimulation with 10nM) and concentration-dependent increase in norepinephrine release with pEC50and Emax(% of basal) values of 8.78±0.17 (1.65nM) and 138±2%, respectively. UII also evoked dopamine, serotonin and histamine release with similar pEC50values. UII increased glutamate release but only at high concentrations (<100nM) and this failed to saturate. UII markedly increased [Ca2+]iin HEK293-rUT cells in a concentration-dependent manner with pEC50of 8.26±0.24. The UT antagonist UFP-803 reversed both UII-increased norepinephrine release from the cerebrocortical slices (pKB=8.98) and [Ca2+]i(pKB=8.87) in HEK293-rUT cells. Collectively these data suggest that UII evokes the release of norepinephrine via UT receptor activation and produces similar effects on other wakefulness-promoting neurotransmitters: these neurochemical actions of UII may be important for the control of the sleep–wake cycle.