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

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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