Serotonergic regulation of distention-induced ATP release from the urothelium
Serotonergic regulation of distention-induced ATP release from the urothelium
复制标题
DOI：
10.1152/ajprenal.00024.2015
复制
发表时间：
2016-04-01
影响因子：
4.2
通讯作者：
Kawatani, Masahito
中科院分区：
文献类型：
--
作者：
Matsumoto-Miyai, Kazumasa;Yamada, Erika;Kawatani, Masahito
血清素[5-羟色胺（5-HT）]参与中空器官，特别是胃肠道的运动和感觉功能。然而，5-羟色胺参与膀胱内脏感觉仍然未知。由于扩张诱导的ATP释放从尿路上皮起着至关重要的作用，膀胱内脏感觉，我们研究了5-HT信号系统的调控尿路上皮ATP释放。RT-PCR和免疫组织化学分析显示，5-HT 1D和5-HT 4受体的特异性表达。在无膀胱扩张的情况下，5-HT的加入并不影响尿路上皮ATP的释放，但在尿液储存期间，5-HT显著减少了生理压力（5 cmH（2）O）引起的扩张诱导的ATP释放。5-HT对扩张引起的ATP释放的抑制作用可被5-HT 1B/1D拮抗剂GR-127935阻断，但不能被5-HT 4拮抗剂SB-204070阻断。通过巢式RT-PCR扩增在膀胱中检测到编码色氨酸羟化酶1的mRNA，并且L-色氨酸或选择性5-羟色胺再摄取抑制剂西酞普兰也抑制ATP释放，表明5-HT在膀胱中内源性合成和释放。GR-127935的加入显著增强了扩张后40分钟的扩张引起的ATP释放，而SB-204070减少了扩张后20分钟的ATP释放量。这些数据表明，5-HT 4促进扩张诱导的ATP释放在早期阶段，而5-HT 1D抑制ATP释放在后期阶段。5-HT的净抑制效应表明，5-HT对尿路刺激的作用主要是由5-HT 1D介导的。
Serotonin [5-hydroxytryptamine (5-HT)] is involved in both motor and sensory functions in hollow organs, especially in the gastrointestinal tract. However, the involvement of 5-HT in visceral sensation of the urinary bladder remains unknown. Because distention-induced ATP release from the urothelium plays an essential role in visceral sensation of the urinary bladder, we investigated the regulation of urothelial ATP release by the 5-HT signaling system. RT-PCR and immunohistochemical analyses of the urothelium revealed specific expression of 5-HT1D and 5-HT4 receptors. The addition of 5-HT did not affect urothelial ATP release without bladder distention, but it significantly reduced distention-induced ATP release by physiological pressure during urine storage (5 cmH(2)O). The inhibitory effect of 5-HT on distention-elicited ATP release was blocked by preincubation with the 5-HT1B/1D antagonist GR-127935 but not by the 5-HT4 antagonist SB-204070. mRNA encoding tryptophan hydroxylase 1 was detected in the urinary bladder by nested RT-PCR amplification, and L-tryptophan or the selective serotonin reuptake inhibitor citalopram also inhibited ATP release, indicating that 5-HT is endogenously synthesized and released in the urinary bladder. The addition of GR-127935 significantly enhanced the distention-elicited ATP release 40 min after distention, whereas SB-204070 reduced the amount of ATP release 20 min after distention. These data suggest that 5-HT4 facilitates the distention-induced ATP release at an earlier stage, whereas 5-HT1D inhibits ATP release at a later stage. The net inhibitory effect of 5-HT indicates that the action of 5-HT on the urothelium is mediated predominantly by 5-HT1D.