Activation of uroepithelial 5-HT(4)R inhibits mechanosensory activity of murine bladder afferent nerves.
Activation of uroepithelial 5-HT(4)R inhibits mechanosensory activity of murine bladder afferent nerves.
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尿上皮 5-HT4R 的激活抑制小鼠膀胱传入神经的机械感觉活动
DOI：
10.3389/fphys.2022.990178
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发表时间：
2022
影响因子：
4
通讯作者：
Rong W
中科院分区：
文献类型：
--
作者：
Lu Y;Li J;Dong L;Luo P;Zhang G;Rong W
Serotonin (5-HT) is known to act via multiple 5-HT receptors at spinal and supraspinal levels to regulate micturition. However, the contribution of peripheral 5-HT and its receptors in bladder physiology and pathology is not very well understood, despite evidence showing expression of multiple 5-HT receptors in the bladder wall and 5-HT may activate bladder afferent nerves. The current study was designed to investigate the possible role of 5-HT4R in modulation of the sensitivity of bladder afferents to bladder filling. Immunofluorescent staining showed abundant 5-HT4R immunoreactivity largely confined to the uroepithelium in wild type (WT) but not 5-HT4R−/− mice. In the ex vivo bladder-pelvic nerve preparation, intravesical application of the 5-HT4R agonist RS67333 (1–30 μm) caused concentration-dependent decreases of the pelvic nerve response to bladder filling. Such effect was not observed in the presence of 5-HT4R antagonist GR125487 or in 5-HT4R−/− preparations. A cohort of 5-HT4R−/− and WT control mice were treated with intraperitoneal injections of cyclophosphamide (CYP) (75 mg/kg, three times at 2 days interval) to induce chronic cystitis. Void spot analysis showed that CYP-treated 5-HT4R−/− mice urinated more frequently than their CYP-treated WT counterparts. Concomitantly, bladder afferents of CYP-treated 5-HT4R−/− mice displayed exaggerated sensitivity to bladder filling in comparison with the CYP-treated WT controls. These data suggest that 5-HT4R expressed on uroepithelial cells plays an inhibitory role in mechanosensory transduction in the bladder. Loss of 5-HT4R-mediated inhibition may enhance bladder afferent sensitivity and exacerbate bladder overactivity in pathological conditions. We propose that 5-HT4R agonists might be exploited for the treatment of overactive and painful bladder symptoms.
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影响因子：
4.6
作者：
Ueda N;Kondo M;Takezawa K;Kiuchi H;Sekii Y;Inagaki Y;Soda T;Fukuhara S;Fujita K;Uemura M;Imamura R;Miyagawa Y;Nonomura N;Shimada S
通讯作者：
Shimada S
影响因子：
3.1
作者：
Girard, Beatrice M.;Tompkins, John D.;Parsons, Rodney L.;May, Victor;Vizzard, Margaret A.
通讯作者：
Vizzard, Margaret A.
影响因子：
2
作者：
Garba, Kamaluddeen;Avery, Miriam;Lwaleed, Bashir A.
通讯作者：
Lwaleed, Bashir A.
影响因子：
23.4
作者：
Daly, Donna M.;Chess-Williams, Russell;Grundy, David
通讯作者：
Grundy, David
影响因子：
3.8
作者：
Michishita, Mai;Tomita, Ken-ichi;Kasahara, Ken-ichi
通讯作者：
Kasahara, Ken-ichi