P2X₂ and P2X₃ receptor expression in human bladder urothelium and changes in interstitial cystitis

Abstract

OBJECTIVE To investigate whether the expression of P2X3 receptors (implicated in the pathophysiology of pain) is altered in human bladder urothelium from patients with interstitial cystitis (IC, a major symptom of which is pain), and as P2X2 receptors can be co‐expressed with P2X3 receptors, to assess their expression also. PATIENTS AND METHODS Bladder tissue samples were collected from patients undergoing cystectomy or radical prostatectomy. Patients with IC were diagnosed using the international criteria. RNA protein expression levels of both receptors were evaluated using reverse transcription‐polymerase chain reaction (PCR), real‐time quantitative PCR and Western blot analysis. RESULTS P2X2 was expressed in the human urothelium, in a glycosylated form. There was less gene expression of P2X3 in IC urothelium, whereas P2X2 gene expression was unchanged. This contrasted with the protein expression, which was increased for both P2X2 and P2X3. CONCLUSION This is the first report of the expression of the P2X2 receptor in human bladder urothelium. There was greater protein expression of both P2X2 and P2X3 in IC bladder urothelium which did not directly correlate with the gene expression. Changes in expression of P2X2 and P2X3 receptors may contribute to the pain that patients with IC have, and might provide novel drug targets.

Cyclophosphamide-Induced Bladder Inflammation Sensitizes and Enhances P2X Receptor Function in Rat Bladder Sensory Neurons

“…For example, both P2X 2 and P2X 3 receptor knockout mice exhibit bladder hyporeflexia (Cockayne et al 2000(Cockayne et al , 2005 and recordings from bladder primary afferent fibers show attenuated responses to mechanical bladder stimulation (Vlaskovska et al 2001). P2X 2 and P2X 3 receptor expression is increased in the urothelium of IC patients (Tempest et al 2004). …”

Expression of purinergic P2X2-receptors in neurogenic bladder dysfunction due to spinal cord injury: a preliminary immunohistochemical study

“…This finding confirms previous results from localization studies in animals 17 and humans. 7,8 The data presented here demonstrate that P 2 X 2 receptors are frequently expressed in neurogenic detrusor overactivity. Moreover, we found P 2 X 2 receptor expression in idiopathic detrusor overactivity in 72% of the specimens, confirming previous findings that this receptor subtype is frequently expressed in tissues from overactive detrusors.…”

“…15 Also, in patients with interstitial cystitis, P 2 X 2 receptor expression was unchanged when compared to normal detrusor tissue, whereas P 2 X 3 receptor expression was decreased. 7 Thus, the only condition altering P 2 X 2 receptor expression was idiopathic detrusor overactivity. Comparing expression in detrusor overactivity and in bladder dysfunction caused by suprasacral spinal cord injury (SCI) may, therefore, aid in answering the question if the P 2 X 2 receptors are predominantly interacting with bladder control on neuronal or muscular level.…”

“…6 The homomeric P 2 X 3 receptor and the heteromeric P 2 X 2/3 receptor seem to be involved in bladder sensory dysfunction and in bladder pain, for example, in interstitial cystitis. 7 Moreover, P 2 X receptors play a role in detrusor motor function as well. In patients with idiopathic overactive bladder (OAB), an increased expression of the P 2 X 2 subtype protein 8 and a loss of P 2 X 3 and P 2 X 5 proteins have been described.…”

Pirt reduces bladder overactivity by inhibiting purinergic receptor P2X3

“…P2X3-null mice exhibit a marked urinary bladder hyporeflexia, characterized by decreased voiding frequency and increased bladder capacity 11 . Moreover, Tempest et al 23 have reported that P2X3 subunit expression changed greatly in patients with interstitial cystitis. Thus, P2X3 signalling is very important in the regulation of bladder function.…”