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Advances in the Purinergic System
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Advances in the Purinergic System

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 April 2026 | Viewed by 1239

Special Issue Editor

Dr. Margarete Dulce Bagatini

E-Mail Website
Guest Editor
Graduate Program in Medical Sciences, Federal University of Fronteira Sul, Chapecó 89815-899, SC, Brazil
Interests: oxidative stress; purinergic system; inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The purinergic system plays a crucial role in various physiological and pathological processes, including neurotransmission, inflammation, pain, and immune response. In recent years, significant advances have expanded our understanding of the functions and mechanisms of purinergic receptors and their implications in neurodegenerative, cardiovascular diseases, and cancer. This Special Issue aims to gather research articles and reviews that explore new discoveries and therapeutic approaches related to the Purinergic System. We welcome studies on the identification of novel ligands, the development of new drugs, as well as investigations into the modulation of purinergic receptors in pathological contexts. This thematic Special Issue seeks to highlight the most recent scientific contributions that may open new avenues for disease treatment and provide a comprehensive overview of advances in the field of purinergic signaling.

Dr. Margarete Dulce Bagatini
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • purinergic system
  • receptors
  • ectonucleotidases
  • CD39
  • CD73
  • purinergic signaling

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Published Papers (2 papers)

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Research

21 pages, 8839 KB  
Article
Prostaglandins Regulate Urinary Purines by Modulating Soluble Nucleotidase Release in the Bladder Lumen
by Mahsa Borhani Peikani, Alejandro Gutierrez Cruz, Zoe S. Buckley and Violeta N. Mutafova-Yambolieva
Int. J. Mol. Sci. 2025, 26(16), 8023; https://doi.org/10.3390/ijms26168023 - 19 Aug 2025
Viewed by 411
Abstract
Distention of the urinary bladder wall during filling stretches the urothelium and induces the release of chemical mediators, including adenosine 5′-triphosphate (ATP) and prostaglandins (PGs), that transmit signals between cells within the bladder wall. The urothelium also releases soluble nucleotidases (s-NTDs) that control [...] Read more.
Distention of the urinary bladder wall during filling stretches the urothelium and induces the release of chemical mediators, including adenosine 5′-triphosphate (ATP) and prostaglandins (PGs), that transmit signals between cells within the bladder wall. The urothelium also releases soluble nucleotidases (s-NTDs) that control the availability of ATP and its metabolites at receptor sites in umbrella cells and cells deeper in the bladder wall, as well as in the urine. This study investigated whether PGs regulate the intravesical breakdown of ATP by s-NTDs. Using a murine decentralized mucosa-only bladder model and an HPLC technology with fluorescence detection, we evaluated the decrease in ATP and increase in ADP, AMP, and adenosine (ADO) in intraluminal solutions (ILS) collected at the end of physiological bladder filling. PGD2, PGE2, and PGI2, but not PGF2α, inhibited the conversion of AMP (produced from ATP) to ADO, likely due to a suppressed intravesical release of s-AMPases. The effects of exogenous PGD2, PGE2, and PGI2 were mediated by DP1/DP2, EP2, and IP prostanoid receptors, respectively. Activation of either DP1 or DP2 receptors by endogenous PGD2 also led to AMP increase and ADO decrease in ILS-containing ATP substrate. Finally, PGs produced by either COX-1 or COX-2 inhibited the hydrolysis of AMP to ADO. Together, these observations suggest that (1) endogenous PGs (chiefly PGD2, and to lesser degree PGE2 and PGI2) allow release of s-NTDs like s-ATPases and s-ADPases but impede the formation of ADO from intravesical ATP by inhibiting the release of s-NTDs/s-AMPases; (2) it is possible that high concentrations of PGD2, PGE2 and PGI2, as anticipated in inflammation or bladder pain syndrome, delay the ADO production and prolong the action of excitatory purine mediators; and (3) either COX-1 and COX-2 are constitutively expressed in the mouse bladder mucosa or COX-2 is induced by distention of the urothelium during bladder filling. Full article
(This article belongs to the Special Issue Advances in the Purinergic System)
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16 pages, 1359 KB  
Article
Dysregulation of Purinergic Signaling Sustains Chronic Inflammation and Oxidative Imbalance in Patients After PitNET Surgical Resection
by Geile Fistarol, Luiz A. de Oliveira, Gilnei B. da Silva, Daiane Manica, Marceli C. Hanauer, Paula Dallagnol, Rafael A. Narzetti, Maria L. Bergamini, Vitória C. de Melo, Tais Vidal, Micheli M. Pillat, Jussara de Lima, Marcelo L. V. da Cunha, Marielle L. Makiyama, Filomena Marafon, Aniela P. Kempka, Ariane Zamoner and Margarete D. Bagatini
Int. J. Mol. Sci. 2025, 26(14), 6890; https://doi.org/10.3390/ijms26146890 - 17 Jul 2025
Viewed by 414
Abstract
Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial tumors. Evidence suggests that these types of tumors may have high recurrence rates. In this context, the purinergic system, oxidative stress, and inflammation are important signaling pathways involved in the cancer’s pathophysiology. This study [...] Read more.
Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial tumors. Evidence suggests that these types of tumors may have high recurrence rates. In this context, the purinergic system, oxidative stress, and inflammation are important signaling pathways involved in the cancer’s pathophysiology. This study aimed to evaluate the sociodemographic and diagnostic profiles, as well as assess the purinergic signaling, immunological, and redox profiles, of patients after PitNET resection. We collected sociodemographic data and the patients’ diagnostic profiles. We also collected blood samples to analyze glycemia, triglycerides, albumin, and ATP levels. The ectonucleotidase activity was determined in peripheral blood mononuclear cells (PBMCs). In addition, we evaluated their redox and immunological profiles. There was a prevalence of gonadotropic macroadenoma derived from PIT-1 cells. We found that patients included in the PitNET group had increased glycemia, serum ATP levels, and ATP hydrolysis in PBMCs. Analyzing their immunological profiles, we found that patients had increased levels of IL-6, IL-10, and TNF, while the IL-27 level was decreased. Regarding their redox profiles, PitNET patients had increased levels of ROS and protein carbonylation. Unexpectedly, patients also showed increased levels of non-protein thiols (NPSHs), total thiols (PSHs), and ascorbic acid. Thus, the dysregulation of purinergic signaling sustained chronic inflammation and oxidative imbalance in PitNET patients for a long time after surgical resection. These data suggest that patients with PitNETs require long-term accompanying to prevent cancer recurrence prognosis. The biomarkers highlighted in this study may be good tools to help the medical approaches. Full article
(This article belongs to the Special Issue Advances in the Purinergic System)
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