Distinct purinergic receptor-mediated currents of rat oculomotor integrator neurons characterized by different firing patterns

2021 ◽  
Vol 126 (4) ◽  
pp. 1045-1054
Author(s):  
Yasuhiko Saito ◽  
Taketoshi Sugimura
Keyword(s):  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Hypoglossal Nucleus ◽  
Gaze Control ◽  
Interstitial Nucleus Of Cajal ◽  
Firing Patterns ◽  
Different Types ◽  
Vertical Gaze ◽  
Purinergic Modulation

The roles of purinergic signaling on vertical (mediated by the interstitial nucleus of Cajal; INC) and horizontal (prepositus hypoglossal nucleus; PHN) gaze control are not understood. Here, we report three current types induced by ATP in INC neurons; the distribution of these current types across different types of INC neurons is different from that in PHN neurons. These results suggest distinct modes of purinergic modulation in horizontal and vertical gaze control centers.

scholarly journals Altered Purinergic Receptor Sensitivity in Type 2 Diabetes-Associated Endothelial Dysfunction and Up4A-Mediated Vascular Contraction

2018 ◽  
Vol 19 (12) ◽  
pp. 3942 ◽  
Author(s):  
Ali Mahdi ◽  
Tong Jiao ◽  
Yahor Tratsiakovich ◽  
Jiangning Yang ◽  
Claes-Göran Östenson ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Function ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Mesenteric Arteries ◽  
Vascular Contraction ◽  
Gk Rats ◽  
Vasoconstrictor Response

Purinergic signaling may be altered in diabetes accounting for endothelial dysfunction. Uridine adenosine tetraphosphate (Up4A), a novel dinucleotide substance, regulates vascular function via both purinergic P1 and P2 receptors (PR). Up4A enhances vascular contraction in isolated arteries of diabetic rats likely through P2R. However, the precise involvement of PRs in endothelial dysfunction and the vasoconstrictor response to Up4A in diabetes has not been fully elucidated. We tested whether inhibition of PRs improved endothelial function and attenuated Up4A-mediated vascular contraction using both aortas and mesenteric arteries of type 2 diabetic (T2D) Goto Kakizaki (GK) rats vs. control Wistar (WT) rats. Endothelium-dependent (EDR) but not endothelium-independent relaxation was significantly impaired in both aortas and mesenteric arteries from GK vs. WT rats. Non-selective inhibition of P1R or P2R significantly improved EDR in aortas but not mesenteric arteries from GK rats. Inhibition of A1R, P2X7R, or P2Y6R significantly improved EDR in aortas. Vasoconstrictor response to Up4A was enhanced in aortas but not mesenteric arteries of GK vs. WT rats via involvement of A1R and P2X7R but not P2Y6R. Depletion of major endothelial component nitric oxide enhanced Up4A-induced aortic contraction to a similar extent between WT and GK rats. No significant differences in protein levels of A1R, P2X7R, and P2Y6R in aortas from GK and WT rats were observed. These data suggest that altered PR sensitivity accounts for endothelial dysfunction in aortas in diabetes. Modulating PRs may represent a potential therapy for improving endothelial function.

scholarly journals P2X7receptors mediate deleterious renal epithelial-fibroblast cross talk

2011 ◽  
Vol 300 (1) ◽  
pp. F62-F70 ◽  
Author(s):  
Murugavel Ponnusamy ◽  
Li Ma ◽  
Rujun Gong ◽  
Maoyin Pang ◽  
Y. Eugene Chin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pyridoxal Phosphate ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Kidney Injury ◽  
Fibroblast Cell ◽  
Underlying Mechanism ◽  
Disulfonic Acid ◽  
Small Interference Rna ◽  
Renal Epithelial Cells

Peritubular fibroblasts in the kidney are the major erythropoietin-producing cells and also contribute to renal repair following acute kidney injury (AKI). Although few fibroblasts were observed in the interstitium adjacent to damaged tubular epithelium in the early phase of AKI, the underlying mechanism by which their numbers were reduced remains unknown. In this study, we tested the hypothesis that damaged renal epithelial cells directly induce renal interstitial fibroblast death by releasing intracellular ATP and activating purinergic signaling. Exposure of a cultured rat renal interstitial fibroblast cell line (NRK-49F) to necrotic renal proximal tubular cells (RPTC) lysate or supernatant induced NRK-49F cell death by apoptosis and necrosis. Depletion of ATP with apyrase or inhibition of the P2X purinergic receptor with pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid blocked the deleterious effect of necrotic RPTC supernatant. The P2X7receptor, an ATP-sensitive purinergic receptor, was not detected in cultured NRK-49F cells but was inducible by necrotic RPTC supernatant. Treatment with A438079, a highly selective P2X7receptor inhibitor, or knockdown of the P2X7receptor with small interference RNA diminished renal fibroblast death induced by necrotic RPTC supernatant. Conversely, overexpression of the P2X7receptor potentiated this response. Collectively, these findings provide strong evidence that damaged renal epithelial cells can directly induce the death of renal interstitial fibroblasts by ATP activation of the P2X7receptor.

4. Adaptive Gaze Control in an Observational Learning Task

2016 ◽  
Author(s):  
James Kim
Keyword(s):  
Eye Movement ◽  
Observational Learning ◽  
Eye Gaze ◽  
Relevant Information ◽  
Learning Task ◽  
Gaze Control ◽  
Visually Guided ◽  
Object Condition ◽  
Learning Tasks ◽  
Different Types

The purpose of this study was to examine factors that influence how people look at objects they will have to act upon while watching others interact with them first. We investigated whether including different types of task-relevant information into an observational learning task would result in participants adapting their gaze towards an object with more task-relevant information. The participant watched an actor simultaneously lift and replace two objects with two hands then was cued to lift one of the two objects. The objects had the potential to change weight between each trial. In our cue condition, participants were cued to lift one of the objects every single time. In our object condition, the participants were cued equally to act on both objects; however, the weights of only one of the objects would have the potential to change. The hypothesis in the cue condition was that the participant would look significantly more at the object being cued. The hypothesis for the object condition was that the participant would look significantly more (i.e. adapt their gaze) at the object changing weight. The rationale behind this is that participants will learn to allocate their gaze significantly more towards that object so they can gain information about its properties (i.e. weight change). Pending results will indicate whether or not this occurred, and has implications for understanding eye movement sequences in visually guided behaviour tasks. The outcome of this study also has implications for the mechanisms of eye gaze with respect to social learning tasks. 

P2Y2 purinergic receptor is induced following human cytomegalovirus infection and its activity is required for efficient viral replication

2016 ◽  
Author(s):  
Saisai Chen ◽  
Thomas Shenk ◽  
Maciej T. Nogalski
Keyword(s):  
Viral Replication ◽  
Host Cell ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Receptor Expression ◽  
Receptor Activity ◽  
P2y2 Receptor ◽  
Infected Cells

AbstractHuman cytomegalovirus (HCMV) manipulates many aspects of host cell biology to create an intracellular milieu optimally supportive of its replication and spread. The current study reveals a role for purinergic signaling in HCMV infection. The levels of several components of the purinergic signaling system, including the P2Y2 receptor, were altered in HCMV-infected fibroblasts. P2Y2 receptor RNA and protein are strongly induced following infection. Pharmacological inhibition of receptor activity or knockdown of receptor expression markedly reduced the production of infectious HCMV progeny. When P2Y2 activity was inhibited, the accumulation of most viral RNAs tested and viral DNA was reduced. In addition, the level of cytosolic calcium within infected cells was reduced when P2Y2 signaling was blocked. The HCMV-coded UL37x1 protein was previously shown to induce calcium flux from the smooth endoplasmic reticulum to the cytosol, and the present study demonstrates that P2Y2 function is required for this mobilization. We conclude that P2Y2 supports the production of HCMV progeny, possibly at multiple points within the viral replication cycle that interface with signaling pathways induced by the purinergic receptor.ImportanceHCMV infection is ubiquitous and can cause life-threatening disease in immunocompromised patients, debilitating birth defects in newborns, and has been increasingly associated with a wide range of chronic conditions. Such broad clinical implications result from the modulation of multiple host cell processes. This study documents that cellular purinergic signaling is usurped in HCMV-infected cells and that the function of this signaling axis is critical for efficient HCMV infection. Therefore, we speculate that blocking P2Y2 receptor activity has the potential to become an attractive novel treatment option for HCMV infection.

Not just uninhibited: Interneurons and seizure onset

2018 ◽  
Vol 10 (468) ◽  
pp. eaav9143 ◽  
Author(s):  
Laura C. Andreae
Keyword(s):  
Rodent Model ◽  
Seizure Onset ◽  
Firing Patterns ◽  
Different Types ◽  
Types Of Interneurons

Optogenetic study in vivo demonstrates that different types of interneurons show consistently elevated but distinct firing patterns in the period preceding seizure onset in a rodent model of epilepsy.

Effect of purinergic receptor activation on Na+-K+ pump activity, excitability, and function in depolarized skeletal muscle

2010 ◽  
Vol 298 (6) ◽  
pp. C1438-C1444 ◽  
Author(s):  
Martin Broch-Lips ◽  
Thomas Holm Pedersen ◽  
Ole Bækgaard Nielsen
Keyword(s):  
Skeletal Muscle ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Receptor Activation ◽  
Control Force ◽  
Fourfold Increase ◽  
Pump Activity ◽  
Force Recovery ◽  
And Function ◽  
Muscle Excitability

Activity-induced elevation of extracellular purines and pyrimidines has been associated with autocrine and paracrine signaling in many tissues. Here we investigate the effect of purinergic signaling for the excitability and contractility of depolarized skeletal muscle. Muscle excitability was experimentally depressed by elevating the extracellular K+ from 4 to 10 mM, which reduced the tetanic force to 24 ± 2% of the force at 4 mM K+. Upon addition of 1 mM ATP, however, the force recovered to 65 ± 8% of the control force ( P < 0.001, n = 5). A similar recovery was seen with ADP, but not with UTP or adenosine. The ATP-induced force recovery could be inhibited by P2Y1 receptor antagonists (3 μM SCH-202676 or 1 μM MRS-2500). A fourfold increase in M-wave area demonstrated that the ATP-induced force recovery was associated with restoration of muscle excitability ( P < 0.05, n = 4). Experiments using 86Rb+ as a tracer for K+ showed that ATP also induced a twofold increase in the activity of muscle Na+-K+ pumps. The force recovery and the stimulation of the Na+-K+ pump activity by ATP were inhibited by 50 μM of the phospholipase C inhibitor U-73122. It is concluded that purinergic signaling can increase the Na+-K+ pump activity and improve force and excitability of depolarized skeletal muscles. This novel purinergic regulation may be important for the maintenance of muscle excitability during intense exercise, where the extracellular K+ can increase substantially.

scholarly journals Secretory functions of macrophages in the human pancreatic islet are regulated by endogenous purinergic signaling

2020 ◽  
Author(s):  
Ada Admin ◽  
Jonathan R. Weitz ◽  
Carol Jacques-Silva ◽  
Mirza Muhammed Fahd Qadir ◽  
Oliver Umland ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Cell Activity ◽  
Human Islet ◽  
Receptor Expression ◽  
Local Source ◽  
Atp Sensing ◽  
Expression Loss ◽  
Secretory Capacity

Endocrine cells of the pancreatic islet interact with their microenvironment to maintain tissue homeostasis. Communication with local macrophages is particularly important in this context, but the homeostatic functions of human islet macrophages are not known. Here we show that the human islet contains macrophages in perivascular regions that are the main local source of the anti-inflammatory cytokine Il-10 and the metalloproteinase MMP9. Macrophage production and secretion of these homeostatic factors is controlled by endogenous purinergic signals. In obese and diabetic states, macrophage expression of purinergic receptors, MMP9, and Il-10 is reduced. We propose that in those states exacerbated beta cell activity due to increased insulin demand and increased cell death produces high levels of ATP that downregulate purinergic receptor expression. Loss of ATP sensing in macrophages may reduce their secretory capacity.

scholarly journals Secretory functions of macrophages in the human pancreatic islet are regulated by endogenous purinergic signaling

2020 ◽  
Author(s):  
Ada Admin ◽  
Jonathan R. Weitz ◽  
Carol Jacques-Silva ◽  
Mirza Muhammed Fahd Qadir ◽  
Oliver Umland ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Cell Activity ◽  
Human Islet ◽  
Receptor Expression ◽  
Local Source ◽  
Atp Sensing ◽  
Expression Loss ◽  
Secretory Capacity

Endocrine cells of the pancreatic islet interact with their microenvironment to maintain tissue homeostasis. Communication with local macrophages is particularly important in this context, but the homeostatic functions of human islet macrophages are not known. Here we show that the human islet contains macrophages in perivascular regions that are the main local source of the anti-inflammatory cytokine Il-10 and the metalloproteinase MMP9. Macrophage production and secretion of these homeostatic factors is controlled by endogenous purinergic signals. In obese and diabetic states, macrophage expression of purinergic receptors, MMP9, and Il-10 is reduced. We propose that in those states exacerbated beta cell activity due to increased insulin demand and increased cell death produces high levels of ATP that downregulate purinergic receptor expression. Loss of ATP sensing in macrophages may reduce their secretory capacity.

scholarly journals Secretory functions of macrophages in the human pancreatic islet are regulated by endogenous purinergic signaling

2020 ◽  
Author(s):  
Ada Admin ◽  
Jonathan R. Weitz ◽  
Carol Jacques-Silva ◽  
Mirza Muhammed Fahd Qadir ◽  
Oliver Umland ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Cell Activity ◽  
Human Islet ◽  
Receptor Expression ◽  
Local Source ◽  
Atp Sensing ◽  
Expression Loss ◽  
Secretory Capacity

Endocrine cells of the pancreatic islet interact with their microenvironment to maintain tissue homeostasis. Communication with local macrophages is particularly important in this context, but the homeostatic functions of human islet macrophages are not known. Here we show that the human islet contains macrophages in perivascular regions that are the main local source of the anti-inflammatory cytokine Il-10 and the metalloproteinase MMP9. Macrophage production and secretion of these homeostatic factors is controlled by endogenous purinergic signals. In obese and diabetic states, macrophage expression of purinergic receptors, MMP9, and Il-10 is reduced. We propose that in those states exacerbated beta cell activity due to increased insulin demand and increased cell death produces high levels of ATP that downregulate purinergic receptor expression. Loss of ATP sensing in macrophages may reduce their secretory capacity.

scholarly journals P2Y2 purinergic receptor modulates virus yield, calcium homeostasis, and cell motility in human cytomegalovirus-infected cells

2019 ◽  
Vol 116 (38) ◽  
pp. 18971-18982 ◽  
Author(s):  
Saisai Chen ◽  
Thomas Shenk ◽  
Maciej T. Nogalski
Keyword(s):  
Cell Motility ◽  
Human Cytomegalovirus ◽  
Cell Biology ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Efficient Production ◽  
Multiple Points ◽  
Viral Spread ◽  
Infected Cells

Human cytomegalovirus (HCMV) manipulates many aspects of host cell biology to create an intracellular milieu optimally supportive of its replication and spread. Our study reveals that levels of several components of the purinergic signaling system, including the P2Y2 and P2X5 receptors, are elevated in HCMV-infected fibroblasts. Knockdown and drug treatment experiments demonstrated that P2Y2 enhances the yield of virus, whereas P2X5 reduces HCMV production. The HCMV IE1 protein induces P2Y2 expression; and P2Y2-mediated signaling is important for efficient HCMV gene expression, DNA synthesis, and the production of infectious HCMV progeny. P2Y2 cooperates with the viral UL37x1 protein to regulate cystolic Ca2+ levels. P2Y2 also regulates PI3K/Akt signaling and infected cell motility. Thus, P2Y2 functions at multiple points within the viral replication cycle to support the efficient production of HCMV progeny, and it may facilitate in vivo viral spread through its role in cell migration.

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