title: Urinary Bladder Relaxation through Activation of Imidazoline Receptors Induced by Agmatine is Increased in Diabetic Rats.
abstract: OBJECTIVE
  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 1 µmol/L acetylcholine (ACh) or 50 mmol/L KCl. Dose-dependent relaxation of the bladder strips was studied by cumulative administration of agmatine 1-100 µmol/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Chi-Mei Medical Center Liouying, Tainan, Taiwan.
authors.forename: Tsung-Chin
authors.initials: TC
authors.lastname: Tsai
authors.affiliation: Department of Urology, Chi-Mei Medical Center Liouying, Tainan, Taiwan.
authors.forename: Chia-Ho
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hsien-Hui
authors.initials: HH
authors.lastname: Chung
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
authors.affiliation: Department of Urology, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: I-Hung
authors.initials: IH
authors.lastname: Chen
authors.affiliation: Department of Urology, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yat-Ching
authors.initials: YC
authors.lastname: Tong
keywords: agmatine; bladder; diabetes; diabetic cystopathy; imidazoline receptors