Urinary bladder relaxation through activation of imidazoline receptors induced by agmatine is increased in diabetic rats

Tsung Chin Tsai, Chia Ho Lin, Hsien Hui Chung, Juei Tang Cheng, I. Hung Chen, Yat Ching Tong

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3 Citations (Scopus)

Abstract

Objectives: The effect of agmatine on bladder contractility and the diabetes-induced alteration of this action were studied in the rat. Methods: Bladder strips were isolated from 9-week-old streptozotocin (STZ)-diabetic rats and control Wistar rats. Strips were hung in an organ bath for measurement of isometric tension and pre-contracted with either 1μmol/L acetylcholine (ACh) or 50mmol/L KCl. Dose-dependent relaxation of the bladder strips was studied by cumulative administration of agmatine 1-100μmol/L into the organ bath. Effects of specific imidazoline receptor (IR) antagonists on the agmatine-induced relaxation were studied. Western blotting analysis was used to measure bladder IR, sulphonylurea receptor (SUR) and inwardly rectifying K+ channel subunit 6.2 (Kir 6.2) protein levels. Results: Agmatine reduced ACh and KCl pre-contracted bladder strip tension in a dose-dependent fashion. Relaxation was significantly increased in STZ-diabetic rats. The relaxation was inhibited by BU224, a selective I2 IR antagonist; but not by efaroxan (I1 IR antagonist) or KU14R (I3 IR antagonist). Moreover, the agmatine-induced relaxation was attenuated by glibenclamide (inhibitor of KATP channel) and H-89 (inhibitor of protein kinase A), but enhanced by 3-isobutyl-1-methylxanthine (IBMX, inhibitor of cyclic AMP phosphodiesterase). Western blotting showed increased expression of bladder IR but not SUR or Kir 6.2 in the STZ-diabetic rat. Conclusion: Agmatine causes rat bladder relaxation by activation of the I2 IR, which opens KATP channels through the cyclic AMP/protein kinase A pathway. Agmatine-induced bladder relaxation in STZ-diabetic rats is increased due to a higher expression of IR.

Original languageEnglish
Pages (from-to)117-123
Number of pages7
JournalLUTS: Lower Urinary Tract Symptoms
Volume6
Issue number2
DOIs
Publication statusPublished - 2014 Jan 1

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All Science Journal Classification (ASJC) codes

  • Neurology
  • Urology

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