P2X receptors and their role in female idiopathic detrusor instability

Purpose: It is clear from previous studies that adenosine triphosphate is released as a contractile co-transmitter with acetylcholine from parasympathetic nerves supplying the mammalian bladder but the physiological significance of ligand gated purinergic P2X receptors in human bladder innervation has not been adequately investigated. We examined the role of these receptors in female patients with idiopathic detrusor instability. Materials and Methods: Female patients with idiopathic detrusor instability were recruited for cystoscopy and bladder biopsy with ethics approval. Control tissue was obtained from age and sex matched patients with a urodynamically proved stable bladder. We obtained 4 bladder biopsies per patient from the posterior wall. Samples were analyzed in an organ bath for functional studies of the detrusor muscle to assess the purinergic contribution to its contraction. In addition, we performed quantitative analysis using reverse transcriptase-polymerase chain reaction and immunohistochemical localization of P2X receptors. Results: In patients with idiopathic detrusor instability detrusor P2X(2) receptors were significantly elevated, while other P2X receptor subtypes were significantly decreased. A purinergic component of nerve mediated contractions was not detected in control female bladder biopsy specimens but there was a significant component in unstable bladder specimens. It was particularly prominent at stimulation frequencies of 2 to 16 Hz. which are likely to be most relevant physiologically. Approximately 50% of nerve mediated contractions were purinergic in idiopathic detrusor instability cases. Conclusions: In patients with idiopathic detrusor instability there is abnormal purinergic transmission in the bladder, which may explain symptoms. This pathway may be a novel target for the pharmacological treatment of overactive bladder.