title: Expressions of urothelial functional proteins in idiopathic detrusor overactivity patients refractory to antimuscarinic therapy with different urodynamic characteristics.
abstract: OBJECTIVE
  This study investigated the expressions of PGP9.5, P2X3, muscarinic receptor (M3) and beta-3 adrenoreceptor (AR) in idiopathic detrusor overactivity (IDO) patients refractory to antimuscarinic treatment, and analyzed the correlation between protein expressions and clinical symptoms of IDO bladders with different urodynamic characteristics.
  
  
  METHODS
  Specimens of 48 IDO and 10 control patients without lower urinary tract symptoms were included. The levels of these proteins from bladder mucosa were determined by Western blotting.
  
  
  RESULTS
  The expression levels of β3-AR and M3 receptor were similar between IDO patients and controls. When IDO patients were divided into two subgroups, phasic DO and terminal DO, the results showed that β3-AR level in the patients with phasic DO was significantly higher than that of the controls and terminal DO (Both P < 0.05). PGP9.5 and P2X3levels were also significantly increased in phasic DO subgroup than controls. P2X3receptor was positively correlated with PGP9.5 and β3-AR, and negatively correlated with the first sensation of bladder filling and voided volume in phasic DO.
  
  
  CONCLUSIONS
  Similar expression M3 receptor and increased P2X3levels in phasic DO, compared with the controls, indicate that dysregulation of purinergic bladder signaling may contribute to the pathogenesis of phasic DO refractory to antimuscarinics. Elevated expression of β3-AR in phasic DO but not in terminal DO patients may explain the different urodynamic characteristics of DO between the two subgroups. Our findings suggest that β3-AR agonist or P2X3antagonist might be a good treatment choice for patients with phasic DO refractory to antimuscarinic therapy.
authors.affiliation: PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.|Voiding Dysfunction Therapeutic Center, Department of Medical Research, Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: Hsin-Tzu
authors.initials: HT
authors.lastname: Liu
authors.affiliation: Voiding Dysfunction Therapeutic Center, Department of Medical Research, Tzu Chi General Hospital, Hualien, Taiwan.|Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
authors.forename: Hann-Chorng
authors.initials: HC
authors.lastname: Kuo
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D001750:Urinary Bladder, Neurogenic / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000378:metabolism*; D014563:Urodynamics; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism*
chemical_list: C568534:ADRB3 protein, human; D018727:Muscarinic Antagonists; D043587:Receptor, Muscarinic M3; D022702:Receptors, Adrenergic, beta-3
keywords: P2 X 3 receptor; beta-3 adrenoreceptor; idiopathic detrusor overactivity; urothelial functional protein