P2X and P2Y Receptors—Role in the Pathophysiology of the Nervous System

Puchałowicz, Kamila; Tarnowski, Maciej; Baranowska-Bosiacka, Irena; Chlubek, Dariusz; Dziedziejko, Violetta

doi:10.3390/ijms151223672

Cited by 77 publications

(51 citation statements)

References 170 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this has not been shown to be a cause of enhanced DNA damage resistance. The distinct purine receptor representation in cancer-and non-malignant cells could explain the difference in cellular response [34]. Other explanation could be difference in purine-inactivating cell surface enzymes between ECs and cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Extracellular ATP protects endothelial cells against DNA damage

Aho

Helenius

Vattulainen-Collanus

et al. 2016

Purinergic Signalling

View full text Add to dashboard Cite

Cell damage can lead to rapid release of ATP to extracellular space resulting in dramatic change in local ATP concentration. Evolutionary, this has been considered as a danger signal leading to adaptive responses in adjacent cells.Our aim was to demonstrate that elevated extracellular ATP or inhibition of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1/CD39) activity could be used to increase tolerance against DNA-damaging conditions. Human endothelial cells, with increased extracellular ATP concentration in cell proximity, were more resistant to irradiation or chemically induced DNA damage evaluated with the DNA damage markers γH2AX and phosphorylated p53. In our rat models of DNA damage, inhibiting CD39-driven ATP hydrolysis with POM-1 protected the heart and lung tissues against chemically induced DNA damage. Interestingly, the phenomenon could not be replicated in cancer cells. Our results show that transient increase in extracellular ATP can promote resistance to DNA damage.

show abstract

Section: Discussionmentioning

confidence: 99%

Extracellular ATP protects endothelial cells against DNA damage

Aho

Helenius

Vattulainen-Collanus

et al. 2016

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…They are expressed in many cell types, including immune, microglia, and glial cells, and have roles in immune and inflammation pathways. Recent reviews describe the many functional roles that these receptors could play in mood disorders and pain in animals and humans . Among the signaling targets are the transcription factor NFKB1 and downstream cytokines such as TNFA and IL10.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Factor Analysis to Differentiate Pathways Linked to Fibromyalgia, Chronic Fatigue Syndrome, and Depression in a Diverse Patient Sample

Iacob

Light

Donaldson

et al. 2015

Arthritis Care & Research

View full text Add to dashboard Cite

Objective To determine if independent candidate genes can be grouped into meaningful biological factors and if these factors are associated with the diagnosis of chronic fatigue syndrome (CFS) and fibromyalgia (FMS) while controlling for co-morbid depression, sex, and age. Methods We included leukocyte mRNA gene expression from a total of 261 individuals including healthy controls (n=61), patients with FMS only (n=15), CFS only (n=33), co-morbid CFS and FMS (n=79), and medication-resistant (n=42) or medication-responsive (n=31) depression. We used Exploratory Factor Analysis (EFA) on 34 candidate genes to determine factor scores and regression analysis to examine if these factors were associated with specific diagnoses. Results EFA resulted in four independent factors with minimal overlap of genes between factors explaining 51% of the variance. We labeled these factors by function as: 1) Purinergic and cellular modulators; 2) Neuronal growth and immune function; 3) Nociception and stress mediators; 4) Energy and mitochondrial function. Regression analysis predicting these biological factors using FMS, CFS, depression severity, age, and sex revealed that greater expression in Factors 1 and 3 was positively associated with CFS and negatively associated with depression severity (QIDS score), but not associated with FMS. Conclusion Expression of candidate genes can be grouped into meaningful clusters, and CFS and depression are associated with the same 2 clusters but in opposite directions when controlling for co-morbid FMS. Given high co-morbid disease and interrelationships between biomarkers, EFA may help determine patient subgroups in this population based on gene expression.

show abstract

“…Accordingly, anandamide induces both panicolytic and panicogenic effects in rats via its actions at cannabinoid receptor 1 and TRPV1, respectively (37). In the nociceptive system, P2Y receptors (40) and serotonergic signaling (41) are examples for such antagonistic responses to the same mediator. So are P2Y 1 , P2Y 12 , P2Y 13 , and P2Y 14 receptors expressed in neurons of mouse dorsal root ganglia (42) that can act either pronociceptively (P2Y 1 ) or antinociceptively (P2Y 12 , P2Y 13 , and P2Y 14 ) (40).…”

Section: Discussionmentioning

confidence: 99%

The leukotriene B4 receptors BLT1 and BLT2 form an antagonistic sensitizing system in peripheral sensory neurons

Zinn

Sisignano

Kern

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

Sensitization of the heat-activated ion channel transient receptor potential vanilloid 1 (TRPV1) through lipids is a fundamental mechanism during inflammation-induced peripheral sensitization. Leukotriene B4 is a proinflammatory lipid mediator whose role in peripheral nociceptive sensitization is not well understood to date. Two major G-protein-coupled receptors for leukotriene B4 have been identified: the high-affinity receptor BLT1 and the low-affinity receptor BLT2. Transcriptional screening for the expression G-protein-coupled receptors in murine dorsal root ganglia showed that both receptors were among the highest expressed in dorsal root ganglia. Calcium imaging revealed a sensitization of TRPV1-mediated calcium increases in a relative narrow concentration range for leukotriene B4 (100-200 nm). Selective antagonists and neurons from knock-out mice demonstrated a BLT1-dependent sensitization of TRPV1-mediated calcium increases. Accordingly, leukotriene B4-induced thermal hyperalgesia was mediated through BLT1 and TRPV1 as shown using the respective knock-out mice. Importantly, higher leukotriene B4 concentrations (>0.5 μm) and BLT2 agonists abolished sensitization of the TRPV1-mediated calcium increases. Also, BLT2 activation inhibited protein kinase C- and protein kinase A-mediated sensitization processes through the phosphatase calcineurin. Consequently, a selective BLT2-receptor agonist increased thermal and mechanical withdrawal thresholds during zymosan-induced inflammation. In accordance with these data, immunohistochemical analysis showed that both leukotriene B4 receptors were expressed in peripheral sensory neurons. Thus, the data show that the two leukotriene B4 receptors have opposing roles in the sensitization of peripheral sensory neurons forming a self-restricting system.

show abstract

P2X and P2Y Receptors—Role in the Pathophysiology of the Nervous System

Cited by 77 publications

References 170 publications

Extracellular ATP protects endothelial cells against DNA damage

Extracellular ATP protects endothelial cells against DNA damage

Gene Expression Factor Analysis to Differentiate Pathways Linked to Fibromyalgia, Chronic Fatigue Syndrome, and Depression in a Diverse Patient Sample

The leukotriene B4 receptors BLT1 and BLT2 form an antagonistic sensitizing system in peripheral sensory neurons

Contact Info

Product

Resources

About