The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures. Export

@article{citeulike:5720673, abstract = {Transient receptor potential channels have recently been implicated in physiological functions in a urogenital system. In this study, we investigated the role of transient receptor potential vanilloid 4 (TRPV4) channels in a stretch sensing mechanism in mouse primary urothelial cell cultures. The selective TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate (4alpha-PDD) evoked Ca(2+) influx in wild-type (WT) urothelial cells, but not in TRPV4-deficient (TRPV4KO) cells. We established a cell-stretch system to investigate stretch-evoked changes in intracellular Ca(2+) concentration and ATP release. Stretch stimulation evoked intracellular Ca(2+) increases in a stretch speed- and distance-dependent manner in WT and TRPV4KO cells. In TRPV4KO urothelial cells, however, the intracellular Ca(2+) increase in response to stretch stimulation was significantly attenuated compared with that in WT cells. Stretch-evoked Ca(2+) increases in WT urothelium were partially reduced in the presence of ruthenium red, a broad TRP channel blocker, whereas that in TRPV4KO cells did not show such reduction. Potent ATP release occurred following stretch stimulation or 4alpha-PDD administration in WT urothelial cells, which was dramatically suppressed in TRPV4KO cells. Stretch-dependent ATP release was almost completely eliminated in the presence of ruthenium red or in the absence of extracellular Ca(2+). These results suggest that TRPV4 senses distension of the bladder urothelium, which is converted to an ATP signal in the micturition reflex pathway during urine storage.}, author = {Mochizuki, Tsutomu and Sokabe, Takaaki and Araki, Isao and Fujishita, Kayoko and Shibasaki, Koji and Uchida, Kunitoshi and Naruse, Keiji and Koizumi, Schuichi and Takeda, Masayuki and Tominaga, Makoto}, citeulike-article-id = {5720673}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M109.020206}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19531473}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19531473}, day = {7}, doi = {10.1074/jbc.M109.020206}, issn = {0021-9258}, journal = {The Journal of biological chemistry}, keywords = {trpv4, urology}, month = {August}, number = {32}, pages = {21257--21264}, posted-at = {2009-09-04 05:38:54}, priority = {2}, title = {The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures.}, url = {http://dx.doi.org/10.1074/jbc.M109.020206}, volume = {284}, year = {2009} }

TY - JOUR ID - citeulike:5720673 L3 - citeulike-article-id:5720673 N2 - Transient receptor potential channels have recently been implicated in physiological functions in a urogenital system. In this study, we investigated the role of transient receptor potential vanilloid 4 (TRPV4) channels in a stretch sensing mechanism in mouse primary urothelial cell cultures. The selective TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate (4alpha-PDD) evoked Ca(2+) influx in wild-type (WT) urothelial cells, but not in TRPV4-deficient (TRPV4KO) cells. We established a cell-stretch system to investigate stretch-evoked changes in intracellular Ca(2+) concentration and ATP release. Stretch stimulation evoked intracellular Ca(2+) increases in a stretch speed- and distance-dependent manner in WT and TRPV4KO cells. In TRPV4KO urothelial cells, however, the intracellular Ca(2+) increase in response to stretch stimulation was significantly attenuated compared with that in WT cells. Stretch-evoked Ca(2+) increases in WT urothelium were partially reduced in the presence of ruthenium red, a broad TRP channel blocker, whereas that in TRPV4KO cells did not show such reduction. Potent ATP release occurred following stretch stimulation or 4alpha-PDD administration in WT urothelial cells, which was dramatically suppressed in TRPV4KO cells. Stretch-dependent ATP release was almost completely eliminated in the presence of ruthenium red or in the absence of extracellular Ca(2+). These results suggest that TRPV4 senses distension of the bladder urothelium, which is converted to an ATP signal in the micturition reflex pathway during urine storage. IS - 32 JF - The Journal of biological chemistry SN - 0021-9258 EP - 21264 TI - The TRPV4 cation channel mediates stretch-evoked Ca2+ influx and ATP release in primary urothelial cell cultures. VL - 284 SP - 21257 KW - trpv4 KW - urology AU - Mochizuki, Tsutomu AU - Sokabe, Takaaki AU - Araki, Isao AU - Fujishita, Kayoko AU - Shibasaki, Koji AU - Uchida, Kunitoshi AU - Naruse, Keiji AU - Koizumi, Schuichi AU - Takeda, Masayuki AU - Tominaga, Makoto PY - 2009/08/07/ UR - http://dx.doi.org/10.1074/jbc.M109.020206 ER -