Orexinergic neurons and barbiturate anesthesia
Orexinergic neurons and barbiturate anesthesia
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DOI：
10.1016/s0306-4522(03)00554-2
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Matsuki, A
中科院分区：
文献类型：
--
作者：
Kushikata, T;Hirota, K;Matsuki, A
食欲素(OXS)调节睡眠，可能与大脑去甲肾上腺素能神经元相互作用。此外，去甲肾上腺素能活动影响巴比妥酸盐麻醉。由于我们最近也报道了OXS选择性地引起大鼠大脑脑片去甲肾上腺素的释放，我们假设巴比妥酸盐的麻醉可能是由于与中枢食欲素能系统的相互作用而产生的。为了验证这一假设，我们在大鼠身上进行了一系列体内和体外研究。在体内，I.C.V.的作用。观察OXA、OX1受体拮抗剂SB-334867-A对戊巴比妥、硫喷妥钠和苯巴比妥诱导的麻醉时间(翻正反射消失)的影响。体外实验观察了巴比妥酸盐和SB-334867-A对OX诱发的大鼠大脑皮层脑片去甲肾上腺素释放的影响。在表达人OX1/OX2受体的中国仓鼠卵巢细胞中，用和不用巴比妥类药物时，OX A和B引起的细胞内钙离子增加。OX A和B显著减少了戊巴比妥、硫喷妥钠和苯巴比妥的麻醉时间15-40%。SB-334867-A可使硫喷妥钠诱导的麻醉时间延长约40%，并逆转OX A所致麻醉时间的减少。在体外，所有麻醉剂巴比妥酸盐均可抑制OX诱导的去甲肾上腺素释放，其IC50值与临床相关。GABA(A)拮抗剂荷包牡丹碱不能改变硫喷妥钠的抑制作用，而GABA(A)激动剂Muscimol不能抑制去甲肾上腺素的释放。此外，巴比妥类药物与OX或OX2受体均无相互作用。综上所述，我们的数据提示食欲素能神经元可能是巴比妥类药物的重要靶点，而GABA(A)、OX1和OX2受体可能不参与这种相互作用。(C)2003年IBRO。爱思唯尔有限公司出版。保留所有权利。
Orexins (OXs) regulate sleep with possible interactions with brain noradrenergic neurons. In addition, noradrenergic activity affects barbiturate anesthesia. As we have also recently reported that OXs selectively evoke norepinephrine release from rat cerebrocortical slices we hypothesized that barbiturate anesthesia may result from of an interaction with central orexinergic systems.To test this hypothesis, we performed a series of in vivo and in vitro studies in rats. In vivo, the effects of i.c.v. OX A, B and SB-334867-A (OX1 receptor antagonist) on pentobarbital, thiopental or phenobarbital-induced anesthesia times (loss of righting reflex) was assessed. In vitro effects of barbiturates and SB-334867-A on OX-evoked norepinephrine release from cerebrocortical slice was examined. In Chinese hamster ovary cells expressing human OX1/OX2 receptors OX A- and B-evoked increases in intracellular Ca2+ were measured with and without barbituratesOX A and B significantly decreased pentobarbital, thiopental and phenobarbital anesthesia times by 15-40%. SB-334867-A increased thiopental-induced anesthesia time by approximately by 40%, and reversed the decrease produced by OX A. In vitro, all anesthetic barbiturates inhibited OX-evoked norepinephrine release with clinically relevant IC50 values. A GABA(A) antagonist, bicuculline, did not modify the inhibitory effects of thiopental and the GABA(A) agonist, muscimol, did not inhibit norepinephrine release. In addition there was no interaction of barbiturates with either OX, or OX2 receptors.Collectively our data suggest that orexinergic neurons may be an important target for barbiturates, and GABA(A), OX1 and OX2 receptors may not be involved in this interaction. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.