Uta Daisuke, Hattori Tsuyoshi, Yoshimura Megumu
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama, Japan.
Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Int Neurourol J. 2020 Jun;24(2):127-134. doi: 10.5213/inj.1938248.124. Epub 2020 Jun 30.
Alpha1-adrenoceptors participate in improving storage symptoms of male lower urinary tract symptoms. However, the mechanism of action of these compounds remains unclear. The goal of the present study was to clarify the effect of α1- adrenoceptor antagonists on γ-aminobutyric acid (GABA)/glycine-mediated outward currents of the inhibitory postsynaptic current (IPSC) in substantia gelatinosa (SG) neurons from the lumbosacral spinal cord in rats.
Male adult Sprague-Dawley rats were used. Blind whole-cell patch-clamp recordings were performed in SG neurons from isolated spinal cord slice preparations. IPSCs were recorded in individual SG neurons to which naftopidil (100μM), tamsulosin (100μM), silodosin (30μM), or prazosin (10μM) were applied sequentially with intervening washout periods. Strychnine (2μM), bicuculline (10μM), or tetrodotoxin (TTX)(1μM) were added before naftopidil. Individual outward currents were analyzed.
The bath application of naftopidil, yielded outward IPSCs in 13 of 52 SG neurons. The naftopidil response was unchanged in the presence of TTX. Regression analysis of the outward currents between the 1st and 2nd applications of naftopidil revealed a Pearson correlation coefficient of 0.996 with a line slope of 0.983. The naftopidil-induced outward current was attenuated in the presence of strychnine and/or bicuculline. The GABA/glycine-mediated outward currents induced by tamsulosin, silodosin, and prazosin were smaller than those obtained with naftopidil.
Naftopidil-induced GABA/glycine-mediated outward currents in a subset of SG neurons prepared from the L6- S1 level of rat spinal cord. The results indicated that α1-adrenoceptor antagonists, particularly naftopidil, induce neural suppression (in part) by mediating hyperpolarization. The response is associated with glycinergic and/or GABAergic neural transmission. Naftopidil may suppress the micturition reflex and improve urinary storage symptoms as a subsidiary effect resulting from hyperpolarization in SG neurons of the spinal cord.
α1肾上腺素能受体参与改善男性下尿路症状的储尿期症状。然而，这些化合物的作用机制仍不清楚。本研究的目的是阐明α1肾上腺素能受体拮抗剂对大鼠腰骶部脊髓胶状质（SG）神经元中γ-氨基丁酸（GABA）/甘氨酸介导的抑制性突触后电流（IPSC）外向电流的影响。
使用成年雄性Sprague-Dawley大鼠。在分离的脊髓切片制备物的SG神经元中进行盲法全细胞膜片钳记录。在单个SG神经元中记录IPSC，依次应用萘哌地尔（100μM）、坦索罗辛（100μM）、西洛多辛（30μM）或哌唑嗪（10μM），中间有洗脱期。在萘哌地尔之前加入士的宁（2μM）、荷包牡丹碱（10μM）或河豚毒素（TTX）（1μM）。分析单个外向电流。
浴用萘哌地尔在52个SG神经元中的13个中产生外向IPSC。在存在TTX的情况下，萘哌地尔反应不变。萘哌地尔第一次和第二次应用之间外向电流的回归分析显示皮尔逊相关系数为0.996，直线斜率为0.983。在存在士的宁和/或荷包牡丹碱的情况下，萘哌地尔诱导的外向电流减弱。坦索罗辛、西洛多辛和哌唑嗪诱导的GABA/甘氨酸介导的外向电流小于萘哌地尔获得的电流。
萘哌地尔在大鼠脊髓L6-S1水平制备的一部分SG神经元中诱导GABA/甘氨酸介导的外向电流。结果表明，α1肾上腺素能受体拮抗剂，特别是萘哌地尔，通过介导超极化（部分地）诱导神经抑制。该反应与甘氨酸能和/或GABA能神经传递有关。萘哌地尔可能作为脊髓SG神经元超极化产生的附属效应抑制排尿反射并改善储尿期症状。
