Therapeutic potential of purinergic signalling for diseases of the urinary tract

This review begins with background information about the discovery and conceptual steps contributing to our current knowledge of purinergic signalling. It then deals with several topics concerned with the physiology and pathophysiology of the lower urinary tract, including: the involvement in the voiding reflex of ATP released as a co-transmitter with acetylcholine from parasympathetic nerves supplying the bladder and ATP released from urothelial cells during bladder distension to initiate the voiding reflex via P2X₃ receptors on suburothelial low-threshold sensory nerve fibres; this latter mechanosensory transduction pathway is also involved via high-threshold fibres in the initiation of pain. Treatment of prostate and bladder cancer with ATP not only appears to be effective against the primary tumours, but also improves the systemic symptoms associated with advanced malignancy. There is dual control of the tone of blood vessels: constriction by ATP released as a co-transmitter from sympathetic nerves and vasodilatation via ATP released from endothelial cells during shear stress acting on endothelial P2 receptors to release nitric oxide. A purinergic hypothesis is discussed for the mechanism underlying acupuncture, widely used for the treatment of urinary disorders.