Sensitization of purinergic P2X receptors is one of the mechanisms responsible for exaggerated pain responses to inflammatory injuries. Prostaglandin E2 (PGE2), produced by inflamed tissues, is known to contribute to abnormal pain states. In a previous study, we showed that PGE2 increases fast inactivating ATP currents that are mediated by homomeric P2X3 receptors in dorsal root ganglion (DRG) neurons isolated from normal rats. Protein kinase A (PKA) is the signalling pathway used by PGE2. Little is known about the action of PGE2 on ATP currents after inflammation, although the information is crucial for understanding the mechanisms underlying inflammation-induced sensitization of P2X receptors. We therefore studied the effects of PGE2 on P2X3 receptor-mediated ATP currents in DRG neurons dissociated from complete Freund's adjuvant (CFA)-induced inflamed rats. We found that PGE2 produces a large increase in ATP currents. PKCepsilon, in addition to PKA, becomes involved in the modulatory action of PGE2. Thus, PGE2 signalling switches from a solely PKA-dependent pathway under normal conditions to both PKA- and PKC-dependent pathways after inflammation. Studying the mechanisms underlying the switch, we demonstrated that cAMP-responsive guanine nucleotide exchange factor 1 (Epac1) is up-regulated after inflammation. The Epac agonist CPT-OMe mimics the potentiating effect of PGE2 and occludes the PKC-mediated PGE2 action on ATP currents. These results suggest that Epac plays a critical role in P2X3 sensitization by activation of de novo PKC-dependent signalling of PGE2 after inflammation and would be a useful therapeutic target for pain therapies.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277053 | PMC |
http://dx.doi.org/10.1113/jphysiol.2007.135616 | DOI Listing |
J Colloid Interface Sci
December 2024
Molecular Diagnostic Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou First People's Hospital, Hangzhou 310006, China. Electronic address:
Developing multimodal combination therapy strategies to disrupt the redox homeostasis within tumor cells is currently an important approach in cancer treatment. In this study, we designed and prepared multifunctional composite nanoparticles MPDA-PEG@MnO@2-DG (MPPMD NPs) utilizing mesoporous polydopamine nanoparticles (MPDA NPs) as carriers. These carriers were coated with polyethylene glycol (PEG), and manganese dioxide (MnO) and loaded with 2-deoxy-d-glucose (2-DG).
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
December 2024
Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Missense mutations in calmodulin (CaM)-encoding genes are associated with life-threatening ventricular arrhythmia syndromes. Here, we investigated a role of cardiac K channel dysregulation in arrhythmogenic long QT syndrome (LQTS) using a knock-in mouse model heterozygous for a recurrent mutation (p.N98S) in the gene (Calm1).
View Article and Find Full Text PDFSci Rep
December 2024
Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang city, Jiangxi province, China.
P2X7 receptor (P2X7R) plays a role in regulating tumor progression, but it is unclear whether P2X7R affects the pathological characteristics of patients with gastric cancer and the activity of gastric cancer cells. Therefore, this study preliminarily investigated the relationship between P2X7R and clinicopathological features of patients with gastric cancer, and further explored the effect of P2X7R on the proliferation, migration and invasion of gastric cancer cells through functional experiments. The results showed that P2X7R was highly expressed in gastric cancer tissues and gastric cancer cells.
View Article and Find Full Text PDFWorld J Cardiol
December 2024
Clinical College of Chinese Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China.
The maintenance of intracellular and extracellular adenosine triphosphate (ATP) levels plays a pivotal role in cardiac function. In recent years, burgeoning attention has been directed towards ATP-induced cell death (AICD), revealing it as a distinct cellular demise pathway triggered by heightened extracellular ATP concentrations, distinguishing it from other forms of cell death such as apoptosis and necrosis. AICD is increasingly acknowledged as a critical mechanism mediating the pathogenesis and progression of various cardiovascular maladies, encompassing myocardial ischemia-reperfusion injury, sepsis-induced cardiomyopathy, hypertrophic cardiomyopathy, arrhythmia, and diabetic cardiomyopathy.
View Article and Find Full Text PDFFront Hum Neurosci
December 2024
Division of Clinical Cognitive Sciences, Department of Neurology, RWTH Aachen University Hospital, Aachen, Germany.
Introduction: Anodal transcranial direct current stimulation (tDCS) has been reported to modulate gamma-aminobutyric acid levels and cerebral energy consumption in the brain. This study aims to investigate long-term GABA and cerebral energy modulation following anodal tDCS over the primary motor cortex.
Method: To assess GABA and energy level changes, proton and phosphorus magnetic resonance spectroscopy data were acquired before and after anodal or sham tDCS.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!