Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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The Inhibitory Mechanism on Acetylcholine-Induced Contraction of Bladder Smooth Muscle in the Streptozotocin-Induced Diabetic Rat

  • Han, Jong Soo (Signaling and Pharmacological Activity Research Lab, College of Pharmacy, Chung-Ang University) ;
  • Kim, Su Jin (Signaling and Pharmacological Activity Research Lab, College of Pharmacy, Chung-Ang University) ;
  • Nam, Yoonjin (Signaling and Pharmacological Activity Research Lab, College of Pharmacy, Chung-Ang University) ;
  • Lee, Hak Yeong (Signaling and Pharmacological Activity Research Lab, College of Pharmacy, Chung-Ang University) ;
  • Kim, Geon Min (Signaling and Pharmacological Activity Research Lab, College of Pharmacy, Chung-Ang University) ;
  • Kim, Dong Min (Signaling and Pharmacological Activity Research Lab, College of Pharmacy, Chung-Ang University) ;
  • Sohn, Uy Dong (Signaling and Pharmacological Activity Research Lab, College of Pharmacy, Chung-Ang University)
  • Received : 2018.07.23
  • Accepted : 2018.09.20
  • Published : 2019.01.01
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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 $A_1$ receptor antagonist), udenafil (a PDE5 inhibitor), prazosin (an ${\alpha}_1$-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 $Ca^{2+}$ release mediated by PLC/IP3 and PDE5 activity were responsible for decreased bladder smooth muscle contractility in DM rats.

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References

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