Differential Influences of Endogenous and Exogenous Sensory Neuropeptides on the ATP Metabolism by Soluble Ectonucleotidases in the Murine Bladder Lamina Propria.
Differential Influences of Endogenous and Exogenous Sensory Neuropeptides on the ATP Metabolism by Soluble Ectonucleotidases in the Murine Bladder Lamina Propria.
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DOI：
10.3390/ijms242115650
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发表时间：
2023-10-27
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：
Cruz, Alejandro Gutierrez;Aresta Branco, Mafalda S. L.;Peikani, Mahsa Borhani;Mutafova-Yambolieva, Violeta N.
关键词：
膀胱尿道鞘和尿道下膜/固有层（LP）具有突出的感觉和换能器功能，其中传入神经元和尿道鞘衍生的嘌呤介质如腺苷5 '-三磷酸（ATP）、腺苷5'-二磷酸（ADP）和腺苷（ADO）的积极参与。嘌呤在受体靶点的有效浓度显著依赖于胞外核苷酸酶（ENTDs）对ATP的降解。我们最近报道了可溶性ENTDs（s-ENTDs）在LP中的调节释放以及随之而来的ATP降解为ADP，AMP和ADO。LP中的传入神经元可以被尿路上皮ATP激活并释放肽和其他可以改变其附近细胞活性的递质。采用小鼠离体去逼尿肌膀胱模型，以1，N6-乙烯基-ATP（eATP）为底物，采用灵敏的HPLC-FLD方法，我们发现外源性神经肽降钙素基因相关肽（CGRP）、P物质（Sub P）、神经激肽A（NKA）、和垂体腺苷酸环化酶激活多肽[PACAP（1-38）]均增加s-在LP中自发和/或在膀胱充盈期间释放的ENTD。使用神经肽受体拮抗剂，我们观察到，内源性NKA没有修改的ATP水解的s-ENTDs，而内源性Sub P增加的组成和扩张诱导释放的s-ENTDs。相反，内源性CGRP和PACAP（1-38）增加扩张诱导的s-ENTDs释放，但不增加自发释放。本研究提出了新的想法，在LP的肽能和嘌呤能信号机制之间的相互作用有影响膀胱的兴奋性和功能，通过调节在LP的效应细胞的腺嘌呤嘌呤的有效浓度。
Bladder urothelium and suburothelium/lamina propria (LP) have prominent sensory and transducer functions with the active participation of afferent neurons and urothelium-derived purine mediators such as adenosine 5’-triphosphate (ATP), adenosine 5’-diphosphate (ADP), and adenosine (ADO). Effective concentrations of purines at receptor targets depend significantly on the extracellular degradation of ATP by ectonucleotidases (ENTDs). We recently reported the regulated release of soluble ENTDs (s-ENTDs) in the LP and the consequent degradation of ATP to ADP, AMP, and ADO. Afferent neurons in the LP can be activated by urothelial ATP and release peptides and other transmitters that can alter the activity of cells in their vicinity. Using a murine decentralized ex vivo detrusor-free bladder model, 1,N6-etheno-ATP (eATP) as substrate, and sensitive HPLC-FLD methodologies, we found that exogenous neuropeptides calcitonin gene-related peptide (CGRP), substance P (Sub P), neurokinin A (NKA), and pituitary adenylate cyclase-activating polypeptide [PACAP (1-38)] all increased the degradation of eATP by s-ENTDs that were released in the LP spontaneously and/or during bladder filling. Using antagonists of neuropeptide receptors, we observed that endogenous NKA did not modify the ATP hydrolysis by s-ENTDs, whereas endogenous Sub P increased both the constitutive and distention-induced release of s-ENTDs. In contrast, endogenous CGRP and PACAP (1-38) increased the distention-induced, but not the spontaneous, release of s-ENTDs. The present study puts forward the novel idea that interactions between peptidergic and purinergic signaling mechanisms in the LP have an impact on bladder excitability and functions by regulating the effective concentrations of adenine purines at effector cells in the LP.
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影响因子：
5.6
作者：
通讯作者：
--
影响因子：
5.6
作者：
Aresta Branco, Mafalda S. L.;Cruz, Alejandro Gutierrez;Peikani, Mahsa Borhani;Mutafova-Yambolieva, Violeta N.
通讯作者：
Mutafova-Yambolieva, Violeta N.
影响因子：
5.5
作者：
Ferguson, DR;Kennedy, I;Burton, TJ
通讯作者：
Burton, TJ
影响因子：
2.9
作者：
Bobalova, J;Bobal, P;Mutafova-Yambolieva, VN
通讯作者：
Mutafova-Yambolieva, VN
影响因子：
--
作者：
Alexander, Tyla I.;Tasma, Zoe;Walker, Christopher S.
通讯作者：
Walker, Christopher S.