Expressions of urothelial functional proteins in idiopathic detrusor overactivity patients refractory to antimuscarinic therapy with different urodynamic characteristics.

AIMS: This study investigated the expressions of PGP9.5, P2  X 3 , 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 P2  X 3 levels were also significantly increased in phasic DO subgroup than controls. P2  X 3 receptor 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 P2  X 3 levels 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 P2  X 3 antagonist might be a good treatment choice for patients with phasic DO refractory to antimuscarinic therapy.