Urothelium update: how the bladder mucosa measures bladder filling

This review critically evaluates the evidence on mechanoreceptors and pathways in the bladder urothelium that are involved in normal bladder filling signalling.

Evidence from in vitro and in vivo studies on (i) signalling pathways like the adenosine triphosphate pathway, cholinergic pathway and nitric oxide and adrenergic pathway, and (ii) different urothelial receptors that are involved in bladder filling signalling like purinergic receptors, sodium channels and TRP channels will be evaluated. Other potential pathways and receptors will also be discussed.

Bladder filling results in continuous changes in bladder wall stretch and exposure to urine. Both barrier and afferent signalling functions in the urothelium are constantly adapting to cope with these dynamics. Current evidence shows that the bladder mucosa hosts essential pathways and receptors that mediate bladder filling signalling. Intracellular calcium ion increase is a dominant factor in this signalling process. However, there is still no complete understanding how interacting receptors and pathways create a bladder filling signal. Currently, there are still novel receptors investigated that could also be participating in bladder filling signalling.

Normal bladder filling sensation is dependent on multiple interacting mechanoreceptors and signalling pathways. Research efforts need to focus on how these pathways and receptors interact to fully understand normal bladder filling signalling.