Urinary ATP Levels Are Controlled by Nucleotidases Released from the Urothelium in a Regulated Manner.
Urinary ATP Levels Are Controlled by Nucleotidases Released from the Urothelium in a Regulated Manner.
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DOI：
10.3390/metabo13010030
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发表时间：
2022-12-24
期刊：
影响因子：
4.1
通讯作者：
中科院分区：
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腺苷5‘-三磷酸(ATP)在充盈过程中会在膀胱腔内释放。尿路上皮三磷酸腺苷被认为对膀胱兴奋性有调节作用。由于膀胱过度活动症、间质性膀胱炎或膀胱痛综合征患者尿液中的三磷酸腺苷升高，因此尿三磷酸腺苷被认为是反映膀胱功能障碍的尿液生物标志物。尿三磷酸腺苷的改变也可能与排尿功能障碍有关，与代谢综合征相关的疾病状态有关。细胞外的三磷酸腺苷水平由三磷酸腺苷的释放以及膜结合和可溶性核苷酸酶(S-NTDS)的三磷酸腺苷水解酶决定。目前尚不清楚S-NTDS是否对尿三磷酸腺苷有调节作用。利用亚乙基-三磷酸腺苷底物和高效液相色谱-荧光检测技术，我们发现S-纳米管在体外小鼠无逼尿肌膀胱的管腔内释放。用蛋白质毛细管免疫电泳法测定，在充填结束时收集的管腔内溶液(ILS)含有ENTPD3和GT；ENPP1和GT；ENPP3ENTPD2=NT5E=ALPL/≥。腺苷环化酶的激活可增加S纳米管的释放，而AC抑制剂SQ22536对此无影响。相反，福司可林减少和SQ22536增加S-NTDS在固有层的释放。腺苷可促进ILS和固有层中S-NTDS的释放，并加速ATP的水解。因此，在充盈过程中，S-NTDS在膀胱腔内有一个受调节的释放。在膀胱兴奋性异常的情况下，尿路上皮S-NTDS的异常释放或功能可能导致尿三磷酸腺苷的升高。
Adenosine 5′-triphosphate (ATP) is released in the bladder lumen during filling. Urothelial ATP is presumed to regulate bladder excitability. Urinary ATP is suggested as a urinary biomarker of bladder dysfunctions since ATP is increased in the urine of patients with overactive bladder, interstitial cystitis or bladder pain syndrome. Altered urinary ATP might also be associated with voiding dysfunctions linked to disease states associated with metabolic syndrome. Extracellular ATP levels are determined by ATP release and ATP hydrolysis by membrane-bound and soluble nucleotidases (s-NTDs). It is currently unknown whether s-NTDs regulate urinary ATP. Using etheno-ATP substrate and HPLC-FLD detection techniques, we found that s-NTDs are released in the lumen of ex vivo mouse detrusor-free bladders. Capillary immunoelectrophoresis by ProteinSimple Wes determined that intraluminal solutions (ILS) collected at the end of filling contain ENTPD3 > ENPP1 > ENPP3 ≥ ENTPD2 = NT5E = ALPL/TNAP. Activation of adenylyl cyclase with forskolin increased luminal s-NTDs release whereas the AC inhibitor SQ22536 had no effect. In contrast, forskolin reduced and SQ22536 increased s-NTDs release in the lamina propria. Adenosine enhanced s-NTDs release and accelerated ATP hydrolysis in ILS and lamina propria. Therefore, there is a regulated release of s-NTDs in the bladder lumen during filling. Aberrant release or functions of urothelial s-NTDs might cause elevated urinary ATP in conditions with abnormal bladder excitability.
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影响因子：
19
作者：
Alcedo KP;Bowser JL;Snider NT
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DOI：
10.1152/ajprenal.00112.2021
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影响因子：
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影响因子：
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作者：
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