Yoshizawa Tsuyoshi, Hayashi Yukio, Yoshida Akira, Yoshida Shohei, Ito Yoshihiko, Yamaguchi Kenya, Yamada Shizuo, Takahashi Satoru
Department of Urology, Nihon University School of Medicine, 30-1, Oyaguchikamicho, Itabashi-ku,, Tokyo, 173-8610, Japan.
Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan.
Int Urol Nephrol. 2018 Mar;50(3):451-458. doi: 10.1007/s11255-018-1800-6. Epub 2018 Jan 24.
To investigate time course of bladder dysfunction and concurrent changes in number and affinity of the muscarinic and PX receptor in the early stage of streptozotocin (STZ)-induced diabetic rats.
Diabetic rats were prepared by the intraperitoneal injection of 50 mg/kg of STZ to 7-week-old female Wistar rats. We performed recording of 24-h voiding behavior and cystometry at 1, 4, 8, and 12 weeks after the induction of diabetes. A muscle strip experiments with electrical field stimulation (EFS), carbachol, and α,β-methylene adenosine 5'-triphosphate (α,β-MeATP) were also performed at the same time-points. Additionally, concurrent changes in number and affinity of bladder muscarinic and PX receptor were measured by a radioreceptor assay using [N-methyl-H] scopolamine methyl chloride ([H]NMS) and α,β-methylene-ATP (2,8-H) tetrasodium salt ([H]α,β-MeATP).
In STZ-induced diabetic rats, polydipsic polyuric pollakiuria were noted on recording of 24-h voiding behavior from early stage. Also, the residual urine volume markedly increased in diabetic rats on cystometry. In the muscle strip experiment, the detrusor contractions induced by EFS, carbachol, and α,β-MeATP were enhanced in STZ-induced diabetic rats. Based on the radioreceptor assay, the maximum number of sites (Bmax) for the specific binding of [H]NMS and [H]α,β-MeATP was concurrently increased in the bladder from diabetic rats.
Increased bladder contractility is found in early stage of diabetic rats. Then, bladder dysfunction is associated with increased number of muscarinic and PX receptors in STZ-induced diabetic rats.
研究链脲佐菌素（STZ）诱导的糖尿病大鼠早期膀胱功能障碍的时间进程以及毒蕈碱和嘌呤能受体数量及亲和力的同时变化。
对7周龄雌性Wistar大鼠腹腔注射50mg/kg STZ制备糖尿病大鼠。在诱导糖尿病后1、4、8和12周进行24小时排尿行为记录和膀胱测压。同时在相同时间点进行电场刺激（EFS）、卡巴胆碱和α,β-亚甲基腺苷5'-三磷酸（α,β-MeATP）的肌肉条实验。此外，使用[甲基-H]东莨菪碱甲基氯（[H]NMS）和α,β-亚甲基-ATP（2,8-H）四钠盐（[H]α,β-MeATP）通过放射受体分析测量膀胱毒蕈碱和嘌呤能受体数量及亲和力的同时变化。
在STZ诱导的糖尿病大鼠中，从早期24小时排尿行为记录中可观察到多饮多尿和尿频。膀胱测压显示糖尿病大鼠残余尿量明显增加。在肌肉条实验中，STZ诱导的糖尿病大鼠中EFS、卡巴胆碱和α,β-MeATP诱导的逼尿肌收缩增强。基于放射受体分析，糖尿病大鼠膀胱中[H]NMS和[H]α,β-MeATP特异性结合的最大位点数量（Bmax）同时增加。
在糖尿病大鼠早期发现膀胱收缩力增加。因此，在STZ诱导的糖尿病大鼠中，膀胱功能障碍与毒蕈碱和嘌呤能受体数量增加有关。
