Urothelial ATP signaling: what is its role in bladder sensation?

Bladder functional disorders are common health problems; however, their pathologies are poorly understood. Adenosine triphosphate (ATP) released from the urothelium has been suggested to have an essential role in the micturition reflex, and its involvement in bladder functional disorders has been intensively investigated. Here, we review the latest advances in research on urothelial ATP signaling.

We reviewed research articles on the role of the urothelium and urothelial ATP release in bladder function.

Mice lacking purinergic receptors have been reported to exhibit marked bladder hyporeflexia. Based on this observation, it was commonly believed, according to the widely held ATP urothelial signaling theory, that stretch-induced urothelial ATP release mediates the sensation of bladder filling via purinergic receptors. However, recent studies employing novel experimental methods and approaches have demonstrated that there are no significant differences in bladder function between wild-type and purinergic receptor knockout mice under physiological conditions. Nonetheless, under pathological conditions, inhibition of purinergic receptors has been shown to improve bladder hyperactivity. Moreover, enhanced urothelial ATP release has been reported in patients with bladder functional disorders.

Recently, conflicting evidence has led us to question the role of urothelial ATP signaling in normal micturition reflex. In contrast, under pathological conditions, it seems likely that enhanced urothelial ATP signaling mediates bladder hyperactivity. These recent findings suggest that the urothelial ATP signaling pathway is a potential therapeutic target for bladder functional disorders.