Mechanosensitive release of ATP in the urinary bladder mucosa

The urinary bladder mucosa (urothelium and suburothelium/lamina propria) functions as a barrier between the content of the urine and the underlying bladder tissue. The bladder mucosa is also a mechanosensitive tissue that releases signaling molecules that affect functions of cells in the bladder wall interconnecting the mucosa with the detrusor muscle and the CNS. Adenosine 5'-triphosphate (ATP) is a primary mechanotransduction signal that is released from cells in the bladder mucosa in response to bladder wall distention and activates cell membrane-localized P2X and P2Y purine receptors on urothelial cells, sensory and efferent neurons, interstitial cells, and detrusor smooth muscle cells. The amounts of ATP at active receptor sites depend significantly on the amounts of extracellularly released ATP. Spontaneous and distention-induced release of ATP appear to be under differential control. This review is focused on mechanisms underlying urothelial release of ATP in response to mechanical stimulation. First, we present a brief overview of studies that report mechanosensitive ATP release in bladder cells or tissues. Then, we discuss experimental evidence for mechanosensitive release of urothelial ATP by vesicular and non-vesicular mechanisms and roles of the stretch-activated channels PIEZO channels, transient receptor potential vanilloid type 4, and pannexin 1. This is followed by brief discussion of possible involvement of calcium homeostasis modulator 1, acid-sensing channels, and connexins in the release of urothelial ATP. We conclude with brief discussion of limitations of current research and of needs for further studies to increase our understanding of mechanotransduction in the bladder wall and of purinergic regulation of bladder function.