Biomolecules & Therapeutics  
The Inhibitory Mechanism on Acetylcholine-Induced Contraction of Bladder Smooth Muscle in the Streptozotocin-Induced Diabetic Rat
Jong Soo Han, Su Jin Kim, Yoonjin Nam, Hak Yeong Lee, Geon Min Kim, Dong Min Kim and Uy Dong Sohn*
Signaling and Pharmacological Activity Research Lab, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
E-mail: udsohn@cau.ac.kr
Tel: +82-2-820-5614, Fax: +82-2-826-8752
Received: July 23, 2018; Revised: September 10, 2018; Accepted: September 20, 2018; Published online: November 12, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Most diabetic patients experience diabetic mellitus (DM) urinary bladder dysfunction. A number of studies evaluate bladder smooth muscle contraction in DM. In this study, we evaluated the change of bladder smooth muscle contraction between normal rats and DM rats. Furthermore, we used pharmacological inhibitors to determine the differences in the signaling pathways between normal and DM rats. Rats in the DM group received an intraperitoneal injection of 65 mg/kg streptozotocin and measured blood glucose level after 14 days to confirm DM. Bladder smooth muscle contraction was induced using acetylcholine (ACh, 10–4 M). The materials such as, atropine (a muscarinic receptor antagonist), U73122 (a phospholipase C inhibitor), DPCPX (an adenosine A1 receptor antagonist), udenafil (a PDE5 inhibitor), prazosin (an α1-receptor antagonist), papaverine (a smooth muscle relaxant), verapamil (a calcium channel blocker), and chelerythrine (a protein kinase C inhibitor) were pre-treated in bladder smooth muscle. We found that the DM rats had lower bladder smooth muscle contractility than normal rats. When prazosin, udenafil, verapamil, and U73122 were pre-treated, there were significant differences between normal and DM rats. Taken together, it was concluded that the change of intracellular Ca2+ release mediated by PLC/IP3 and PDE5 activity were responsible for decreased bladder smooth muscle contractility in DM rats.
Keywords: Bladder, Contractility, Diabetes, Smooth muscle, PLC


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