P2 purinergic receptor dysregulation in urologic disease

Maynard, Janielle P.; Sfanos, Karen S.

doi:10.1007/s11302-022-09875-1

Cited by 6 publications

(2 citation statements)

References 159 publications

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“…It was hypothesized that ATP is released from the urothelium into the suburothelium/lamina propria (LP), where it activates afferent neurons and stimulates voiding [ 3 , 4 , 5 , 6 ]. In the following years, it became clear that a broad class of purinergic receptors, including ligand-gated ion channel P2X receptors, G-protein coupled P2Y receptors and G-protein-coupled adenosine receptors, is expressed in all major cell types in the bladder mucosa [ 1 , 7 ]. Therefore, extracellular ATP may contribute to sensory processing through the activation of purinergic receptors on various cell types within the bladder wall, in addition to sensory afferents.…”

Section: Introductionmentioning

confidence: 99%

Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria

Branco

Cruz

Peikani

et al. 2023

IJMS

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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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Section: Introductionmentioning

confidence: 99%

Sensory Neurons, PIEZO Channels and PAC1 Receptors Regulate the Mechanosensitive Release of Soluble Ectonucleotidases in the Murine Urinary Bladder Lamina Propria

Branco

Cruz

Peikani

et al. 2023

IJMS

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“…At the same time, immune cells in the tumor microenvironment can also interact with tumor cells through the Purinergic pathway, thereby affecting tumor cell growth and metastasis [11]. It is noteworthy that Purinergic receptors are abundantly expressed in urological cancers, including KIRC, and that ATP can influence tumor-associated signaling pathways through the Purinergic receptor P2RX6, further promoting the migration and invasion of renal tumors [12,13]. In addition, it has also been demonstrated that the Purinergic receptor P2RX7 is an independent poor prognostic indicator of postoperative survival specific to KIRC patients [14].…”

Section: Introductionmentioning

confidence: 99%

The potential value of the Purinergic pathway in the prognostic assessment and clinical application of kidney renal clear cell carcinoma

Xie,

Wang,

Jiang

et al. 2024

Aging

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The Purinergic pathway is involved in a variety of important physiological processes in living organisms, and previous studies have shown that aberrant expression of the Purinergic pathway may contribute to the development of a variety of cancers, including kidney renal clear cell carcinoma (KIRC). The aim of this study was to delve into the Purinergic pathway in KIRC and to investigate its potential significance in prognostic assessment and clinical treatment. 33 genes associated with the Purinergic pathway were selected for pancancer analysis. Cluster analysis, targeted drug sensitivity analysis and immune cell infiltration analysis were applied to explore the mechanism of Purinergic pathway in KIRC. Using the machine learning process, we found that combining the Lasso+survivalSVM algorithm worked well for predicting survival accuracy in KIRC. We used LASSO regression to pinpoint nine Purinergic genes closely linked to KIRC, using them to create a survival model for KIRC. ROC survival curve was analyzed, and this survival model could effectively predict the survival rate of KIRC patients in the next 5, 7 and 10 years. Further univariate and multivariate Cox regression analyses revealed that age, grading, staging, and risk scores of KIRC patients were significantly associated with their prognostic survival and were identified as independent risk factors for prognosis. The nomogram tool developed through this study can help physicians accurately assess patient prognosis and provide guidance for developing treatment plans. The results of this study may bring new ideas for optimizing the prognostic assessment and therapeutic approaches for KIRC patients.www.aging-us.com AGINGto predict the survival and treatment response of KIRC patients and provide strong support for clinical decision-making is one of the important directions of current kidney cancer research.

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