Role of connexin hemichannels in the bladder outlet obstruction

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462438
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: University of Yamanashi
• Principal Investigator: KAMIYAMA Manabu 山梨大学, 総合研究部, 講師 (90362061)
• Co-Investigator(Renkei-kenkyūsha): SAWADA Norifumi 山梨大学, 総合研究部, 講師 (70402055) ; HANEDA Yaburu 山梨大学, 総合研究部, 助教 (20402068) ; TAKEDA Masayuki 山梨大学, 総合研究部, 教授 (80197318)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 膀胱 / ATP / ギャップ結合 / ヘミチャネル / 酸化ストレス / 機械的刺激 / 膀胱上皮細胞 / 膀胱炎

Outline of Final Research Achievements

This study is aimed to test the potential participation of connexin hemichannels in the control of bladder activity and pathological processes of bladder disorders. The results showed that mechanic stimulation of bladder with the increased volume of saline caused an abrupt release of ATP, which could be largely prevented by hemichannel inhibitors. In cultured urothelial cells, mechanical stimulation with glass beads or activation of TRPV4 channels with agonists caused a hemichannel-dependent release of ATP. Inhibition of hemichannels with CBX also largely prevented oxidative urothelial cells injury. In an in vivo mouse model of bladder cystitis induced by cyclophosphamide, CBX treatment attenuated bladder oxidative stress and inflammation, and improved bladder function. Our study suggests that connexin hemichannel might contribute to the regulation of bladder activity under both physiological and pathological conditions.

Free Research Field

医歯薬学