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Studies on clarification of central mechanisms of micturition reflex aimed for development of new drugs with the strengthening effect on micturition reflex, which are needed in aging society

研究阐明排尿反射的中枢机制，旨在开发老龄化社会所需的增强排尿反射作用的新药

基本信息

批准号：
15390082
负责人：
TAKAHAMA Kazuo
金额：
$ 5.63万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

We previously revealed that glycine might play some roles in the central mechanism of micturition reflex. In this study, we further studied involvement of glycine receptors in the reflex by using electrophysiological, neurochemical and pharmacological techniques.【Results】1)In the periaqueductal gray matter(PAG), two types(type I and type II) of neuronal activity which are related to the micturition reflex, were recorded. One was increased during micturition and another decreased. 2)Both types of neurons were largely located in a narrow PAG region between -8000 and -8300 um of bregma. 3)Type I was located in the ventral part of PAG, whereas type II in the dorsal part of it. 4)In all neurons dissociated from the PAG glycine induced Cl- currents. 5)The characteristics of glycine-induced current were almost similar to those in other central regions such as the spinal cord. 6)The amplitude ratio of glycine- and GABA-induced currents was almost 1. 7)The ratio did not depend on the morphology … More and the location of neurons in ventrolateral PAG. 8)Cloperastine prolonged the closed time without affecting the open time of 5-HT-induced single GIRK channel currents recorded in outside-out mode of the patch clamp. 9)In non-anesthetized rats with infarction of the middle cerebral artery(MCA), bladder capacity(gh), threshold for micturition(Pth), flow rate of urination(rf), bladder compliance(Cp) and micturition latency(Tm) were reduced, and urethral resistant(Ru) was increased. These effects persisted for more than 24 hrs after the infarction. 10)In this period, the expression level of glycine receptor α1 subunit mRNA did not change in the PAG and LDT area. 11)Strychnine(Str) had little effect on the urinary disturbance caused by MCA infarction. But, dextromethorphan(DM) administered 24 hrs after MCA infarction ameliorated parameters of gb and Tm in rats with MCA infarction. 12)Injection of acetic acid solution into the bladder increased the level of Fos protein in the pontine micturition center region of the brainstem including the medial optic area, PAG, Barrington's nucleus(BarN), and the parasympathetic nucleus in the lumbosacral cord. 13)Str and DM depressed the Fos expression in the micturition-related nuclei such as PAG and BarN. Less

我们以前的研究表明，甘氨酸可能在排尿反射的中枢机制中发挥一定的作用。在本研究中，我们进一步研究了甘氨酸受体参与反射的电生理，神经化学和药理学技术。[结果]1）在中脑导水管周围灰质（PAG）内记录到与排尿反射有关的I型和II型神经元活动。一个在排尿时增加，另一个减少。2)这两种类型的神经元主要位于一个狭窄的PAG区域之间的-8000和-8300微米的前囟。3)I型电流位于PAG腹侧，II型电流位于PAG背侧。4）在PAG分离出的神经元中，甘氨酸诱导的Cl-电流均为I型电流。5)甘氨酸诱发电流的特性与脊髓等其他中枢区域的甘氨酸诱发电流的特性基本相似。6)甘氨酸和GABA诱导电流的振幅比几乎为1。7)该比例不依赖于形态 ...更多信息以及PAG腹外侧区神经元的定位。8)氯哌斯汀延长了5-HT诱导的单个GIRK通道电流的关闭时间，而不影响膜片钳外向模式中记录的开放时间。9）大脑中动脉（MCA）梗死后，非麻醉大鼠膀胱容量（gh）、排尿阈值（Pth）、排尿流速（rf）、膀胱顺应性（Cp）和排尿潜伏期（Tm）均降低，尿道阻力（Ru）增加。这些效应在梗塞后持续超过24小时。10）在此期间，PAG和LDT区甘氨酸受体α1亚单位mRNA的表达水平无明显变化。士的宁（Str）对MCA梗塞所致的排尿障碍无明显影响。但在MCA梗死后24小时给予二甲双胍（DM）可改善MCA梗死大鼠的gb和Tm参数。12)膀胱内注射醋酸溶液可增加脑干脑桥排尿中心区Fos蛋白的水平，包括视内侧区、PAG、Barrington核（BarN）和腰骶髓副交感神经核。13)Str和DM可抑制PAG和BarN等排尿相关核团的Fos表达。少