Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats

作者：Imamura Tetsuya^*; Ishizuka Osamu; Ogawa Teruyuki; Yamagishi Takahiro; Yokoyama Hitoshi; Minagawa Tomonori; Nakazawa Masaki; Gautam Sudha Silwal; Nishizawa Osamu

来源：International Journal of Urology, 2014, 21(10): 1051-1058.

DOI：10.1111/iju.12475

• cold stress
• detrusor overactivity
• diabetic mellitus rat
• imidafenacin
• muscarinic receptors

ObjectivesThis study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type2 diabetes mellitus rats.
MethodsTen-week-old female Goto-Kakizaki diabetic rats (n=12) and Wister Kyoto non-diabetic rats (n=12) were maintained on a high-fat diet for 4weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (272 degrees C) for 20min. They were intravenously administered imidafenacin (0.3mg/kg, n=6) or vehicle (n=6). After 5min, the rats were transferred to a low temperature (42 degrees C) for 40min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M-3 and M-2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry.
ResultsIn non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M-3 to M-2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M-3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats.
ConclusionsImidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M-3 receptors partially mediate cold stress-induced detrusor overactivity.

• 出版日期2014-10