The Regulatory Mechanism Underlying ATP Release from Urothelium pp. 203-216
Authors: (Kazumasa Matsumoto-Miyai, Masaru Yoshizumi, Masahito Kawatani, Department of Neurophysiology, Akita University Graduate School of Medicine, Hondo, Akita, Akita, Japan)
Abstract: The epithelial cells of the urinary bladder (urothelium) function as a sensory organ by releasing ATP in response to mechanical/chemical stimuli. Released ATP transmits the signals of bladder extension or nociception to the afferent nerve terminals in the urinary bladder. The urothelium expresses various channels and receptors, which are activated by stretch, swelling, and neurotransmitters. The activation of these channels and/or receptors was shown to regulate the ATP release from the urothelium. First, we summarize the functions of these receptors and/or channels on the urothelial ATP release from previous studies. These studies suggest that the urothelial ATP release could be driven by the Ca2+ influx from extracellular space via channels (e.g., TRPV1, TRPV4) and/or the Ca2+ release from endoplasmic reticulum (ER) downstream of these receptors (e.g., muscarinic receptors, a PGE2 receptor; EP1). Therefore, the function of Ca2+ on the urothelial ATP release was subsequently reviewed. Indeed, the urothelial ATP release was reduced by the removal of extracellular Ca2+ or the blockade of ER-Ca2+ channels, and induced by the agonists of ER-Ca2+ channels. Interestingly, we found the distinct function of extracellular Ca2+ on the ATP release. The increase in extracellular Ca2+ reduced the ATP release from the primary culture of urothelial cells and the isolated urinary bladder tissues. This inhibitory effect might be attributed to the store-operated Ca2+ entry (SOCE), which is induced by the depletion of Ca2+ store in the ER. Finally, we discuss the potential role of SOCE with our recent data, and provide the importance of urothelial ATP release for micturition in this chapter.