Purinergic signalling in the urinary bladder.

It is well established that in most species, exocytotic vesicular release of ATP from parasympathetic neurons contributes to contraction of the bladder. However, ATP is released not only from parasympathetic nerves, but also from the urothelium. During bladder filling, the urothelium is stretched and ATP is released from the umbrella cells thereby activating mechanotransduction pathways. ATP release can also be induced by various mediators present in the urine and and/or released from nerves or other components of the lamina propria. Urothelial release of ATP is mainly attributable to vesicular transport or exocytosis and, to a smaller extent, to pannexin hemichannel conductive efflux. After release, ATP acts on P2X3 and P2X2/3 receptors on suburothelial sensory nerves to initiate the voiding reflex and to mediate the sensation of bladder filling and urgency. ATP also acts on suburothelial interstitial cells/myofibroblasts generating an inward Ca(2+) transient that via gap junctions could provide a mechanism for long-distance spread of signals from the urothelium to the detrusor muscle. ATP release can be affected by urological diseases, e.g., interstitial cystitis and both the mechanisms of release and the receptors activated by ATP may be targets for future drugs for treatment of lower urinary tract disorders.