Tsuyoshi Yoshizawa1, Yukio Hayashi2, Akira Yoshida3, Shohei Yoshida2, Yoshihiko Ito3, Kenya Yamaguchi1, Shizuo Yamada3, Satoru Takahashi4. 1. Department of Urology, Nihon University School of Medicine, 30-1, Oyaguchikamicho, Itabashi-ku,, Tokyo, 173-8610, Japan. 2. Taiho Pharmaceutical Co., Ltd., Tsukuba, Japan. 3. Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. 4. Department of Urology, Nihon University School of Medicine, 30-1, Oyaguchikamicho, Itabashi-ku,, Tokyo, 173-8610, Japan. takahashi.satoru@nihon-u.ac.jp.
Abstract
OBJECTIVES: To investigate time course of bladder dysfunction and concurrent changes in number and affinity of the muscarinic and P2X receptor in the early stage of streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: 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 P2X receptor were measured by a radioreceptor assay using [N-methyl-3H] scopolamine methyl chloride ([3H]NMS) and α,β-methylene-ATP (2,8-3H) tetrasodium salt ([3H]α,β-MeATP). RESULTS: 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 [3H]NMS and [3H]α,β-MeATP was concurrently increased in the bladder from diabetic rats. CONCLUSION: Increased bladder contractility is found in early stage of diabetic rats. Then, bladder dysfunction is associated with increased number of muscarinic and P2X receptors in STZ-induced diabetic rats.
OBJECTIVES: To investigate time course of bladder dysfunction and concurrent changes in number and affinity of the muscarinic and P2X receptor in the early stage of streptozotocin (STZ)-induced diabeticrats. MATERIALS AND METHODS:Diabeticrats were prepared by the intraperitoneal injection of 50 mg/kg of STZto 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 P2X receptor were measured by a radioreceptor assay using [N-methyl-3H] scopolamine methyl chloride ([3H]NMS) and α,β-methylene-ATP (2,8-3H) tetrasodium salt ([3H]α,β-MeATP). RESULTS: In STZ-induced diabeticrats, polydipsic polyuric pollakiuria were noted on recording of 24-h voiding behavior from early stage. Also, the residual urine volume markedly increased in diabeticrats on cystometry. In the muscle strip experiment, the detrusor contractions induced by EFS, carbachol, and α,β-MeATP were enhanced in STZ-induced diabeticrats. Based on the radioreceptor assay, the maximum number of sites (Bmax) for the specific binding of [3H]NMS and [3H]α,β-MeATP was concurrently increased in the bladder from diabeticrats. CONCLUSION: Increased bladder contractility is found in early stage of diabeticrats. Then, bladder dysfunction is associated with increased number of muscarinic and P2X receptors in STZ-induced diabeticrats.
Authors: M Yoshida; Y Homma; A Inadome; M Yono; H Seshita; Y Miyamoto; S Murakami; K Kawabe; S Ueda Journal: Exp Gerontol Date: 2001-01 Impact factor: 4.032
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