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

我们先前发现甘氨酸可能在排尿反射的中枢机制中发挥作用。[结果]1)在中脑导水管周围灰质(PAG)，记录到与排尿反射有关的两种类型的神经元活动(I型和II型)。一个在排尿过程中增加，另一个减少。2)这两种类型的神经元主要分布在-8000~-8300微米之间的PAG区域。3)I型位于PAG腹侧，II型位于PAG背侧。4)在所有从PAG分离的神经元上，甘氨酸诱发氯电流。5)甘氨酸诱发电流的特征与脊髓等其他中枢区域的特征相似。6)甘氨酸和氨基丁酸诱发电流的幅度比几乎为1。7)该比不依赖于形态…。More和神经元在PAG腹外侧区的定位。8)氯哌斯汀延长膜片钳外向记录的5-羟色胺引起的GIRK单通道电流的关闭时间，但不影响其开放时间。9)大脑中动脉梗塞(MCA)非麻醉大鼠，膀胱容量(GH)、排尿阈值(PTH)、尿流率(Rf)、膀胱顺应性(Cp)和排尿潜伏期(Tm)降低，尿阻抗(Ru)增大。这些影响在脑梗塞后持续了24小时以上。10)在此期间，甘氨酸受体α-1亚单位的表达水平在前额叶和下丘脑区无明显变化。11)士的宁(Str)对大脑中动脉梗塞所致的排尿障碍无明显影响。而右美沙芬(DM)能改善MCA梗死大鼠的GB和TM参数。12)膀胱内注射醋酸溶液后，脑干内侧视区、PAG、Barrington‘s核(Barn)和腰骶髓副交感神经核等脑桥排尿中心区Fos蛋白表达增加。13)Str和Dm抑制排尿相关核团如PAG和Barn的Fos表达。较少

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