Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria.
Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria.
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DOI：
10.3390/ijms24087322
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发表时间：
2023-04-15
影响因子：
5.6
通讯作者：
Mutafova-Yambolieva, Violeta N.
中科院分区：
文献类型：
--
作者：
Aresta Branco, Mafalda S. L.;Cruz, Alejandro Gutierrez;Peikani, Mahsa Borhani;Mutafova-Yambolieva, Violeta N.
关键词：
膀胱需要足够浓度的细胞外腺苷5′-三磷酸（ATP）和受体部位的其他嘌呤才能正常工作。通过膜结合和可溶性外核苷酸酶（s-ENTDs）将ATP顺序脱磷酸化为ADP、AMP和腺苷（ADO）对于实现嘌呤介质的合适的细胞外水平是必需的。特别地，S-ENTDs以机械敏感的方式在膀胱尿道下裂/固有层（LP）中释放。使用1，N6-乙烯基-ATP（eATP）作为底物和灵敏的HPLC-FLD方法，我们评估了在底物添加之前的填充期间与离体小鼠逼尿肌游离膀胱的LP接触的溶液中eATP降解为eADP、eAMP和eADO。用河豚毒素和ω-芋螺毒素GVIA抑制神经活性，用GsMTx 4和D-GsMTx 4抑制PIEZO通道，用PACAP 6 -38抑制垂体腺苷酸环化酶激活多肽I型受体（PAC 1），这些都增加了LP中膨胀诱导的而不是自发的s-ENTDs释放。因此，可以想象，这些机制响应于扩张的激活限制了s-ENTDs的进一步释放，并防止ATP的过度水解。总之，这些数据表明，传入神经元，PIEZO通道，PAC 1受体和s-ENTDs形成一个系统，该系统运行高度调节的稳态机制，以维持LP中适当的细胞外嘌呤浓度，并确保膀胱充盈期间正常的膀胱兴奋性。
The urinary bladder requires adequate concentrations of extracellular adenosine 5′-triphosphate (ATP) and other purines at receptor sites to function properly. Sequential dephosphorylation of ATP to ADP, AMP and adenosine (ADO) by membrane-bound and soluble ectonucleotidases (s-ENTDs) is essential for achieving suitable extracellular levels of purine mediators. S-ENTDs, in particular, are released in the bladder suburothelium/lamina propria (LP) in a mechanosensitive manner. Using 1,N6-etheno-ATP (eATP) as substrate and sensitive HPLC-FLD methodology, we evaluated the degradation of eATP to eADP, eAMP and eADO in solutions that were in contact with the LP of ex vivo mouse detrusor-free bladders during filling prior to substrate addition. The inhibition of neural activity with tetrodotoxin and ω-conotoxin GVIA, of PIEZO channels with GsMTx4 and D-GsMTx4 and of the pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1) with PACAP6-38 all increased the distention-induced but not spontaneous release of s-ENTDs in LP. It is conceivable, therefore, that the activation of these mechanisms in response to distention restricts the further release of s-ENTDs and prevents excessive hydrolysis of ATP. Together, these data suggest that afferent neurons, PIEZO channels, PAC1 receptors and s-ENTDs form a system that operates a highly regulated homeostatic mechanism to maintain proper extracellular purine concentrations in the LP and ensure normal bladder excitability during bladder filling.
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DOI：
10.1007/s12031-020-01649-x
发表时间：
2021-08
期刊：
Journal of molecular neuroscience : MN
影响因子：
--
作者：
Girard BM;Campbell SE;Beca KI;Perkins M;Hsiang H;May V;Vizzard MA
通讯作者：
Vizzard MA
影响因子：
5.3
作者：
Sculptoreanu, Adrian;Artim, Debra E.;de Groat, William C.
通讯作者：
de Groat, William C.
影响因子：
3.3
作者：
Alcaino, Constanza;Knutson, Kaitlyn;Beyder, Arthur
通讯作者：
Beyder, Arthur
影响因子：
5.5
作者：
Ferguson, DR;Kennedy, I;Burton, TJ
通讯作者：
Burton, TJ
影响因子：
2.7
作者：
Fry, Christopher H.;McCloskey, Karen D.
通讯作者：
McCloskey, Karen D.