Bromovalerylurea modulates GABAA receptor-mediated inhibitory neurotransmission while inducing sleep.
Bromovalerylurea modulates GABAA receptor-mediated inhibitory neurotransmission while inducing sleep.
复制标题
Bromovalerylurea 在诱导睡眠的同时调节 GABAA 受体介导的抑制性神经传递。
DOI：
10.1016/j.bbrc.2022.11.062
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Tanaka J.
中科院分区：
文献类型：
--
作者：
Takeda H;Yoshimura Y;Takagi M;Sato A;Kihara N;Choudhury ME;Yano H;Tanaka J.
溴代戊酰脲（BU）是一种酰基脲衍生物，最初是作为催眠/镇静剂开发的。我们最近报道，在Wistar大鼠模型中，50 mg/kg剂量的BU通过其对小胶质细胞和巨噬细胞的抗炎作用改善败血症、帕金森病和创伤性脑损伤。然而，由于BU在100多年前被开发出来，其催眠机制和特点知之甚少。在此，我们进行了一项脑电图（EEG）研究，发现BU在Wistar大鼠中以超过125 mg/kg的剂量给药时（而不是50 mg/kg的剂量），显著增加非快速眼动（NREM）睡眠持续时间，并剂量依赖性地减少快速眼动（REM）睡眠持续时间。BU诱导的睡眠特征与巴比妥类、苯二氮卓类和Z类药物等化合物的作用相似，所有这些药物都需要γ-氨基丁酸受体（GABAAR）来发挥催眠/镇静作用。为了研究BU是否能增强GABA能神经传递，我们采用全细胞膜片钳技术记录大鼠皮层脑片锥体神经元自发性GABA能介导的抑制性突触后电流（IPSC）。我们发现BU剂量依赖性地延长IPSC。重要的是，延长的IPSC没有被氟马西尼（一种苯二氮卓类受体拮抗剂）减弱，这表明BU对IPSC的调节是由与苯二氮卓类不同的机制介导的。总之，这些数据阐明了BU催眠作用的基本特征，并表明GABAAR介导的Cl−通量的增强可能是其催眠/镇静活性的一种可能机制。
Bromovalerylurea (BU), an acyl urea derivative, was originally developed as a hypnotic/sedative. We recently reported that BU at a dose of 50 mg/kg ameliorates sepsis, Parkinson's disease, and traumatic brain injury in Wistar rat models through its anti-inflammatory actions on microglia and macrophages. However, since BU was developed more than 100 years ago, its hypnotic mechanism and characteristics are poorly understood. Herein, we conducted an electroencephalogram (EEG) study and found that BU, when administered at a dose of more than 125 mg/kg but not at a dose of 50 mg/kg in Wistar rats, significantly increased non-rapid eye movement (NREM) sleep duration and dose-dependently decreased rapid eye movement (REM) sleep duration. This characteristic of sleep induced by BU is similar to the effect of compounds such as barbiturate, benzodiazepine, and z-drugs, all of which require γ-aminobutyric acidAreceptors (GABAAR) for hypnotic/sedative activity. To investigate whether BU could potentiate GABAAergic neurotransmission, we conducted a whole-cell patch-clamp recording from pyramidal neurons in rat cortical slices to detect spontaneous GABAAR-mediatedinhibitorypostsynapticcurrents(IPSCs). We found that BU dose-dependently prolonged IPSCs. Importantly, the prolonged IPSCs were not attenuated by flumazenil, a benzodiazepine receptor antagonist, suggesting that modulation of IPSCs by BU is mediated by different mechanisms from that of benzodiazepine. Taken together, these data elucidate the basic characteristics of the hypnotic effects of BU and suggest that the enhancement of GABAAR-mediated Cl−flux may be a possible mechanism that contributes to its hypnotic/sedative activity.
登录
查看更多内容
巴比妥类药物与人类 GABAA 受体的相互作用：依赖于受体亚基组合
影响因子：
7.3
作者：
S. Thompson;Paul J. Whiting;K. Wafford
通讯作者：
K. Wafford
用溴化物及其边缘变体治疗婴儿严重肌阵挛性癫痫
影响因子：
5.6
作者：
H. Oguni;Kitami Hayashi;M. Oguni;Akiko Mukahira;Takashi Uehara;Y. Fukuyama;R. Umezu;T. Izumi;M. Hara
通讯作者：
M. Hara
DOI：
10.1007/bf01940972
发表时间：
1907
期刊：
Archiv für experimentelle Pathologie und Pharmakologie
影响因子：
--
作者：
A. V. D. Eeckhout
通讯作者：
A. V. D. Eeckhout
与虚假高氯血症相关的共济失调：幕后黑手。
DOI：
10.1016/j.ajem.2008.09.044
发表时间：
2009
期刊：
The American journal of emergency medicine
影响因子：
--
作者：
Ming;Sung;Hung;Shih
通讯作者：
Shih
(-)戊巴比妥在培养的小鼠脊髓神经元中打开长时间的离子通道。
影响因子：
56.9
作者：
D. Mathers;J. Barker
通讯作者：
J. Barker