Spinal glycine transporter-1 inhibition influences the micturition reflex in urethane-anesthetized rats.
Spinal glycine transporter-1 inhibition influences the micturition reflex in urethane-anesthetized rats.
复制标题
脊髓甘氨酸转运蛋白 1 抑制影响尿烷麻醉大鼠的排尿反射。
DOI：
10.1007/s11255-015-1148-0
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Takenaka A
中科院分区：
文献类型：
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作者：
Honda M;Hikita K;Kawamoto B;Muraoka K;Shimizu S;Saito M;Sejima T;Chancellor MB;Yoshimura N;Takenaka A
目的甘氨酸是中枢神经系统中的抑制性神经递质。到目前为止，已克隆出两种甘氨酸转运蛋白(GlyT)，GlyT-1和GlyT-2。本研究的目的是观察选择性GlyT-1抑制剂对乌拉坦麻醉大鼠排尿反射的影响。方法在乌拉坦麻醉下，对雌性SD大鼠(232~265 mg)进行连续膀胱测压(0.04 mg/min)。在建立稳定的排尿周期后，选择性GlyT-1抑制剂ALX5407被鞘内或脑室注射以评估膀胱活动的变化。结果鞘内注射ALX5407(1、3、10、30μg)后，3μg或更高剂量组收缩间期延长，呈剂量依赖关系。鞘内注射ALX5407(1、3、10和30μg)也可剂量依赖性地提高3μg或更高剂量的压力阈值。而侧脑室注射ALX5407(1、3、10和30μg)后，各剂量组的收缩间期、压力阈值、最大排尿压或基线压、排尿后残余尿量均无明显变化。结论GlyT-1在排尿调节中起重要作用。此外，这些发现表明，在乌拉坦麻醉的大鼠，抑制GlyT-1可以抑制脊髓水平的排尿反射。因此，GlyT-1可能成为治疗膀胱过度活动等膀胱功能障碍的潜在靶点。
PurposeGlycine is an inhibitory neurotransmitter in the central nervous system. So far, two types of glycine transporters (GlyTs), GlyT-1 and GlyT-2, have been cloned. The aim of this study is to investigate the effects of a selective GlyT-1 inhibitor that can increase endogenous glycine concentration on the micturition reflex in urethane-anesthetized rats.MethodsContinuous cystometrograms (0.04 ml/min) were performed in female Sprague–Dawley rats (232–265 g) under urethane anesthesia. After stable micturition cycles were established, ALX5407, a selective GlyT-1 inhibitor, was administered intrathecally or intracerebroventricularly to evaluate changes in bladder activity. Cystometric parameters were recorded and compared before and after drug administration.ResultsIntrathecal administration of ALX5407 (1, 3, 10 and 30 μg) increased intercontraction intervals at doses of 3 μg or higher in a dose-dependent fashion. Intrathecal administration of ALX5407 (1, 3, 10 and 30 μg) also increased pressure threshold at doses of 3 μg or higher in a dose-dependent fashion. However, when ALX5407 (1, 3, 10 and 30 μg) was administered intracerebroventricularly, there were no significant changes in intercontraction intervals, pressure threshold, maximum voiding pressure or baseline pressure or post-void residual urine volume at any doses tested.ConclusionThe results of our study indicate that GlyT-1 plays an important role in the modulation of micturition. Furthermore, these findings indicate that in urethane-anesthetized rats suppression of GlyT-1 can inhibit the micturition reflex at the spinal cord level. Thus, GlyT-1 could be a potential target for the treatment of bladder dysfunction such as overactive bladder.