Article
Neurosciences
Kenneth A. Jacobson, Balaram Pradhan, Zhiwei Wen, Asmita Pramanik
Summary: The discovery and clinical implementation of adenosine, P2Y and P2X receptor modulators have advanced significantly in the past 50 years. Although previous clinical trials of selective ligands have not been successful, there is now a renewed focus on new disease conditions and the development of more selective compounds, as well as the elucidation of new receptor and enzyme structures.
Review
Endocrinology & Metabolism
Nadine Mundt, Lina Kenzler, Marc Spehr
Summary: Adenosine triphosphate (ATP) is not only the essential source of cellular energy, but also functions as an extracellular signal that activates purinergic receptors. Purinergic signaling plays a crucial role in male reproductive system functions, particularly in spermatogenesis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Peter Cuthbertson, Nicholas J. Geraghty, Sam R. Adhikary, Katrina M. Bird, Stephen J. Fuller, Debbie Watson, Ronald Sluyter
Summary: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for blood cancers and other haematological disorders, but may lead to graft-versus-host disease (GVHD). Current treatments for GVHD are limited, highlighting the need for exploring inflammatory factors to identify new treatment targets. Purinergic signalling, including purinergic receptors and ectoenzymes, has been implicated in influencing GVHD development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ryo Koyama, Koichi Iwata, Yoshinori Hayashi, Suzuro Hitomi, Ikuko Shibuta, Akihiko Furukawa, Sayaka Asano, Tadayoshi Kaneko, Yoshiyuki Yonehara, Masamichi Shinoda
Summary: The study revealed that pain in tongue cancer patients is caused by upregulation of PANX1 in microglia in the trigeminal spinal subnucleus caudalis, leading to ATP activation of nociceptive neurons in the Vc and ultimately resulting in tongue cancer pain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Omar Mahmoud, Georgia Biazus Soares, Gil Yosipovitch
Summary: Transient Receptor Potential (TRP) channels, found abundantly in the skin, play a crucial role in the sensory pathways of itch, pain, and inflammation. This review article explores the complex physiology of different TRP channels and their involvement in modulating itch sensation and the pathophysiology of acute and chronic itch conditions. The article also highlights emerging small molecule and topical TRP channel agents as potential anti-pruritic treatments, with some advancing into clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Kenneth A. Jacobson, Adriaan P. IJzerman, Christa E. Mueller
Summary: This review paper explores the historical origins of P2 receptors and adenosine receptor ligands, emphasizing the versatility of common chemical scaffolds for multiple receptor targets. By analyzing structure activity relationships, selective receptor subtype targeting can be achieved, leading to potential therapeutic applications in various diseases.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xiao-Yu Cheng, Shu-Fang Li, Yong Chen, Ying-Jie Zhao, Wei Hu, Chao Lu, Ren-Peng Zhou
Summary: TRPM7 is a channel protein located on the cell membrane that regulates the balance of intracellular Mg2+. It plays an important role in cell proliferation, adhesion, migration, and is directly related to disease occurrence and development.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Angela Dziedzic, Elzbieta Miller, Joanna Saluk-Bijak, Marta Niwald, Michal Bijak
Summary: Epidemiological studies confirm a high risk of ischemic events in secondary-progressive multiple sclerosis (SP MS) patients, which is directly associated with an increased level of pro-thrombotic activity of platelets. The study demonstrated enhanced platelet reactivity in response to adenosine diphosphate (ADP) in SP MS patients compared to controls, suggesting a potential molecular basis for the elevated risk of thromboembolism in MS. Identifying the molecular abnormalities of the platelet P2Y(12) receptor expression and functionality could contribute to the development of prevention and targeted treatment strategies for cardiovascular disorders in MS patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Lok Mun Law, Norazrina Azmi, Ian Charles Paterson, Pei Yuen Ng
Summary: Chemotherapeutic agents like cisplatin often fail to treat advanced stage oral squamous cell carcinoma (OSCC) due to chemoresistance. This study focused on the role of purinergic receptors, specifically P2Y, in OSCC and explored the associated signaling pathways. The findings suggest that extracellular nucleotides have varied downstream effects in OSCC cells with different characteristics, indicating the potential for targeted therapy based on individual needs.
Review
Pharmacology & Pharmacy
Aleksandra Szopa, Katarzyna Socala, Anna Serefko, Urszula Doboszewska, Andrzej Wrobel, Ewa Poleszak, Piotr Wlaz
Summary: Purinergic signaling plays a significant role in depression, with studies suggesting altered adenosine metabolism in depressed patients may serve as a disease biomarker. Research also indicates that manipulation of P1 or P2 receptors, along with selective or nonselective ligands, can impact the development and progression of depression.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Clinical Neurology
Lili Kokoti, Mohammad Al-Mahdi Al-Karagholi, Cherie Amalie Waldorff Nielsen, Messoud Ashina
Summary: This study investigated the effect of the K-ATP channel blocker glibenclamide on levcromakalim-induced headache in healthy volunteers and found that glibenclamide did not attenuate levcromakalim-induced headache. Future studies should further explore the role of different isoforms of sulfonylurea receptor subunits of K-ATP channels in the pathogenesis of headache and migraine.
Article
Biochemistry & Molecular Biology
Hao Li, Wang Jiang, Shi-Rong Zhang, Peng-Cheng Li, Tian-Jiao Li, Wei Jin, Hua-Xiang Xu, Xian-Jun Yu, Liang Liu
Summary: This study found that CD41+/CD62P+ platelets are closely associated with the prognosis of pancreatic ductal adenocarcinoma (PDAC). High levels of CD41+/CD62P+ platelets were correlated with microvascular invasion, advanced AJCC stage, and high CA19-9 level, and independently predicted a poor prognosis for resectable PDAC. Mechanistically, Panx1 in CD41+/CD62P+ platelets promotes PDAC cell invasion and metastasis by enhancing IL-1 beta secretion through the phosphorylation of p38 MAPK. In addition, a novel compound named PC63435 was synthesized, which blocked the Panx1/IL-1 beta pathway and reduced the proportion of CD41+/CD62P+ platelets, leading to the suppression of PDAC tumor invasion and metastasis.
Article
Pharmacology & Pharmacy
Waldemar Schaefer, Tobias Staehler, Carolina Pinto Espinoza, Welbeck Danquah, Jan Hendrik Knop, Bjoern Rissiek, Friedrich Haag, Friedrich Koch-Nolte
Summary: P2X7, an ion channel gated by extracellular ATP, plays important roles in inflammation and apoptosis. Polymorphisms in the P2X7 gene are common, and their frequencies vary among different human populations. Considering P2X7 variants of participants is important in designing clinical trials targeting P2X7.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Chih-Chin Shih, Melissa Chan, Nicholas S. Kirkby, Ivana Vojnovic, Jane A. Mitchell, Paul C. Armstrong, Timothy D. Warner
Summary: The study demonstrates a synergistic relationship between P2Y(12) receptor antagonists and adenosine signaling, with their efficacy partly dependent on the presence of endogenous adenosine. Despite reported differences in their effects upon adenosine reuptake, both prasugrel and ticagrelor show similar synergistic effects on platelet inhibition in the presence of adenosine or NECA.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Michele Genovese, Martina Buccirossi, Daniela Guidone, Rossella De Cegli, Sergio Sarnataro, Diego di Bernardo, Luis J. V. Galietta
Summary: The pharmacological inhibitors of TMEM16A have indirect effects on intracellular Ca2+ handling, which may impact their use as research tools. The mechanism of action of these inhibitors involves altering intracellular Ca2+ levels rather than directly inhibiting TMEM16A.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)