Contractions of normal human bladders are induced primarily by ACH released from cholinergic nerve terminals in the bladder. It has been reported that nonadrenergic, noncholinergic bladder contractions are induced by increases of ATP levels in the human bladder under pathologic conditions such as denervation, bladder outlet obstruction, or idiopathic urge incontinence.
ATP acts on two families of purinergic receptors: an ion channel family (P2X) and a G protein-coupled receptor family (P2Y). P2X3 receptors have also been detected in the wall of the bladder in a suburothelial plexus of afferent nerves. In P2X3 knockout mice, afferent activity induced by bladder distention was significantly reduced.21
In patients with idiopathic detrusor instability, numbers of detrusor P2X2 receptors were significantly elevated, whereas those of other P2X receptor subtypes were significantly decreased.22 There was no detectable purinergic component of nerve-mediated detrusor muscle contractility in normal women without instability. However, there was a significant (approximately 80%) purinergic contractility component in bladder of women with detrusor instability.
In conclusion, the purinergic pathway may be a novel target for the pharmacological treatment of OAB. P2X-receptor antagonists could modulate efferent/afferent activities to treat OAB if receptor subtype-specific agents become available.