scholarly journals Increasing Efficiency of Repetitive Electroacupuncture on Purine- and Acid-Induced Pain During a Three-Week Treatment Schedule

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Li ◽  
Ying Zhang ◽  
Peter Illes ◽  
Yong Tang ◽  
Patrizia Rubini
Keyword(s):  
Acidic Medium ◽  
P2x7 Receptor ◽  
Treatment Schedule ◽  
P2x3 Receptor ◽  
P2x7 Receptors ◽  
Analgesic Treatment ◽  
The World ◽  
Zusanli Acupoint ◽  
Rat Paw ◽  
Important Constituent

Acupuncture (AP) is an important constituent of the therapeutic repertoire of traditional Chinese medicine and has been widely used to alleviate chronic painful conditions all over the world. We studied in rats the efficiency of electroacupuncture (EAP) applied to the Zusanli acupoint (ST36) as an analgesic treatment over a 3-week period of time on purine (α,β-methylene ATP, dibenzoyl-ATP)- and acid (pH 6.0 medium)-induced pain in the rat paw. The two ATP derivatives stimulated P2X3 and P2X7 receptors, respectively, while the slightly acidic medium stimulated the “acid-sensitive ion channel 3” (ASIC3). It was found that the P2X7 receptor and ASIC-mediated pain was counteracted by EAP with greater efficiency at the end than at the beginning of the treatment schedule, while the P2X3 receptor–mediated pain was not. Our findings have important clinical and theoretical consequences, among others, because they are difficult to reconcile with the assumption that AP is primarily due to the release of peripheral and central opioid peptides causing the well-known tolerance to their effects. In consequence, AP is a convenient therapeutic instrument to treat subacute and chronic pain.

scholarly journals Functional Coupling between the P2X7 Receptor and Pannexin-1 Channel in Rat Trigeminal Ganglion Neurons

2021 ◽  
Vol 22 (11) ◽  
pp. 5978
Author(s):  
Hiroyuki Inoue ◽  
Hidetaka Kuroda ◽  
Wataru Ofusa ◽  
Sadao Oyama ◽  
Maki Kimura ◽  
...  
Keyword(s):  
Trigeminal Ganglion ◽  
P2x7 Receptor ◽  
P2x Receptor ◽  
Functional Coupling ◽  
Dependent Manner ◽  
High Concentration ◽  
Receptor Antagonists ◽  
P2x7 Receptors ◽  
Pannexin 1 ◽  
Ganglion Neurons

The ionotropic P2X receptor, P2X7, is believed to regulate and/or generate nociceptive pain, and pain in several neuropathological diseases. Although there is a known relationship between P2X7 receptor activity and pain sensing, its detailed functional properties in trigeminal ganglion (TG) neurons remains unclear. We examined the electrophysiological and pharmacological characteristics of the P2X7 receptor and its functional coupling with other P2X receptors and pannexin-1 (PANX1) channels in primary cultured rat TG neurons, using whole-cell patch-clamp recordings. Application of ATP and Bz-ATP induced long-lasting biphasic inward currents that were more sensitive to extracellular Bz-ATP than ATP, indicating that the current was carried by P2X7 receptors. While the biphasic current densities of the first and second components were increased by Bz-ATP in a concentration dependent manner; current duration was only affected in the second component. These currents were significantly inhibited by P2X7 receptor antagonists, while only the second component was inhibited by P2X1, 3, and 4 receptor antagonists, PANX1 channel inhibitors, and extracellular ATPase. Taken together, our data suggests that autocrine or paracrine signaling via the P2X7-PANX1-P2X receptor/channel complex may play important roles in several pain sensing pathways via long-lasting neuronal activity driven by extracellular high-concentration ATP following tissue damage in the orofacial area.

scholarly journals Purinergic Signaling in Endometriosis-Associated Pain

2020 ◽  
Vol 21 (22) ◽  
pp. 8512
Author(s):  
Carla Trapero ◽  
Mireia Martín-Satué
Keyword(s):  
Atp Hydrolysis ◽  
Current Knowledge ◽  
Purinergic Signaling ◽  
Uterine Cavity ◽  
Nucleotide Receptors ◽  
P2x3 Receptor ◽  
P2x7 Receptors ◽  
Pharmacological Management ◽  
Predominant Symptom ◽  
Therapeutic Tools

Endometriosis is an estrogen-dependent gynecological disease, with an associated chronic inflammatory component, characterized by the presence of endometrial tissue outside the uterine cavity. Its predominant symptom is pain, a condition notably altering the quality of life of women with the disease. This review is intended to exhaustively gather current knowledge on purinergic signaling in endometriosis-associated pain. Altered extracellular ATP hydrolysis, due to changes in ectonucleotidase activity, has been reported in endometriosis; the resulting accumulation of ATP in the endometriotic microenvironment points to sustained activation of nucleotide receptors (P2 receptors) capable of generating a persistent pain message. P2X3 receptor, expressed in sensory neurons, mediates nociceptive, neuropathic, and inflammatory pain, and is enrolled in endometriosis-related pain. Pharmacological inhibition of P2X3 receptor is under evaluation as a pain relief treatment for women with endometriosis. The role of other ATP receptors is also discussed here, e.g., P2X4 and P2X7 receptors, which are involved in inflammatory cell–nerve and microglia–nerve crosstalk, and therefore in inflammatory and neuropathic pain. Adenosine receptors (P1 receptors), by contrast, mainly play antinociceptive and anti-inflammatory roles. Purinome-targeted drugs, including nucleotide receptors and metabolizing enzymes, are potential non-hormonal therapeutic tools for the pharmacological management of endometriosis-related pain.

Adenosine Triphosphate–Induced Shedding of CD23 and L-Selectin (CD62L) From Lymphocytes Is Mediated by the Same Receptor but Different Metalloproteases

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 946-951 ◽  
Author(s):  
B. Gu ◽  
L.J. Bendall ◽  
J.S. Wiley
Keyword(s):  
Adenosine Triphosphate ◽  
Phorbol Ester ◽  
P2x7 Receptor ◽  
Transmembrane Protein ◽  
Lymphocytic Leukemia ◽  
P2x7 Receptors ◽  
Extracellular Adenosine ◽  
Zinc Chelator ◽  
High Concentrations ◽  
American Society

CD23 is a transmembrane protein expressed on the surface of B-lymphocytes that binds IgE, CD21, CD11b, and CD11c. High concentrations of soluble CD23 and L-selectin are found in the serum of patients with B-chronic lymphocytic leukemia (B-CLL). Because extracellular adenosine triphosphate (ATP) causes shedding of L-selectin via activation of P2Z/P2X7 receptors expressed on B-CLL lymphocytes, we studied the effect of ATP on shedding of CD23. ATP-induced shedding of CD23 at an initial rate of 12% of that for L-selectin, whereas the EC50 for ATP was identical (35 μmol/L) for shedding of both molecules. Furthermore, benzoylbenzoyl ATP also produced shedding of CD23 and L-selectin with the same agonist EC50 values for both (10 μmol/L). Inactivation of the P2Z/P2X7 receptor by preincubation with oxidized ATP abolished ATP-induced shedding of both molecules. Moreover, KN-62, the most potent inhibitor for the P2Z/P2X7 receptor, inhibited ATP-induced shedding of both CD23 and L-selectin with the same IC50 (12 nmol/L). Ro 31-9790, a membrane permeant zinc chelator that inhibits the phorbol-ester-stimulated shedding of L-selectin, also inhibited shedding of CD23 from B-CLL lymphocytes. However, the IC50 for this inhibition by Ro31-9790 was different for L-selectin and CD23 (83 v 6 μmol/L, respectively). Although L-selectin was completely shed by incubation of cells with phorbol-ester, CD23 was not lost under these conditions. The data show that extracellular ATP induces shedding of L-selectin and CD23 from B-CLL lymphocytes by an action mediated by the P2Z/P2X7 receptor. However, different membrane metalloproteases seem to mediate the shedding of L-selectin and CD23. © 1998 by The American Society of Hematology.

Functional expression of purinergic P2X7 receptors in pregnant rat myometrium

2010 ◽  
Vol 298 (4) ◽  
pp. R1117-R1124 ◽  
Author(s):  
Hiroshi Miyoshi ◽  
Kaoru Yamaoka ◽  
Satoshi Urabe ◽  
Miho Kodama ◽  
Yoshiki Kudo
Keyword(s):  
P2x7 Receptor ◽  
Uterine Contraction ◽  
Extracellular Atp ◽  
Receptor Expression ◽  
P2x Receptor ◽  
Receptor Subtype ◽  
P2x7 Receptors ◽  
Pregnant Rat ◽  
Myometrial Cells ◽  
Induced Currents

ATP has been reported to enhance the membrane conductance of myometrial cells and uterine contractility. Purinergic P2 receptor expression has been reported in the myometrium, using molecular biology, but the functional identity of the receptor subtype has not been determined. In this study, ATP-induced currents were recorded and characterized in single myometrial cells from pregnant rats using whole cell patch clamping. Extracellular ATP was applied in the range of 10 μM-1 mM and induced currents with an EC50 of 74 μM, with no desensitization, time dependency, or voltage dependency. The currents induced carried multiple monovalent cations, with conductances ranked as K+ > Cs+ > Li+ > Na+. They were activated by P2X receptor agonists, with their effectiveness ranked as 2′,3′- O-(4-benzoylbenzoyl)-ATP >> ATP > αβ-methylene-ATP > 2-methylthio ATP ≥ UTP ≥ GTP > ADP. These currents were blocked by the selective P2X7 receptor antagonist 3-[5-(2,3-dichlorophenyl)-1 H-tetrazol-1-yl]methyl pyridine (A-438079). We therefore concluded that ATP-induced currents in rat myometrial cells crossed cell membranes via P2X7 receptors. We further showed that the ATP-induced currents were blocked by extracellular Mg2+ (IC50 = 0.26 mM). Clinically, administering extracellular Mg2+ is known to inhibit uterine contraction. It therefore seems likely that uterine contraction may be induced by raised extracellular ATP and suppressed via Mg2+ inhibiting P2X7 receptors. Further research is needed into the P2X7 receptor as a therapeutic target in abnormal uterine contraction, as a possible treatment for premature labor.

scholarly journals P2X7 receptor activates extracellular signal-regulated kinases ERK1 and ERK2 independently of Ca2+ influx

2003 ◽  
Vol 374 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Jan AMSTRUP ◽  
Ivana NOVAK
Keyword(s):  
P2x7 Receptor ◽  
Fluorescent Protein ◽  
Expression System ◽  
Receptor Expression ◽  
Nucleotide Receptors ◽  
P2x7 Receptors ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells ◽  
Extracellular Signal

P2X7 nucleotide receptors modulate a spectrum of cellular events in various cells including epithelia, such as exocrine pancreas. Although the pharmacology and channel properties of the P2X7 receptors have been studied intensively, signal transduction pathways are relatively unknown. In this study we applied a heterologous expression system of rat P2X7 receptors in HEK-293 cells. We followed the receptor expression and function using the enhanced green fluorescent protein (EGFP) tag, activation of intracellular proteins and increases in cellular Ca2+. EGFP-P2X7 receptors localized to the plasma membrane, clusters within the membrane and intracellularly. Stimulation of P2X7 receptors in HEK-293 cells led to an activation of extracellular signal-regulated kinases ERK1 and ERK2 and this activation was seen after just 1 min of stimulation with ATP. Using C- and N-terminal P2X7-receptor mutants we show that the N-terminus is important in activation of ERKs, whereas deletion of the last 230 amino acids in the C-terminus did not effect ERK activation. On the other hand, Ca2+ entry was impaired in C-terminal but not in N-terminal mutants. In cell suspensions prepared from rat pancreas we show that P2X7 receptors also activate ERK1 and ERK2, indicating that these signalling pathways are also turned on in native epithelium.

Differential expression of the P2X7 receptor in ovarian surface epithelium during the oestrous cycle in the mouse

2013 ◽  
Vol 25 (7) ◽  
pp. 971 ◽  
Author(s):  
F. G. Vázquez-Cuevas ◽  
A. Cruz-Rico ◽  
E. Garay ◽  
A. García-Carrancá ◽  
D. Pérez-Montiel ◽  
...  
Keyword(s):  
P2x7 Receptor ◽  
Ovarian Surface Epithelium ◽  
Oestrous Cycle ◽  
Receptor Expression ◽  
Surface Epithelium ◽  
Purinergic Signalling ◽  
P2x7 Receptors ◽  
Ovarian Surface ◽  
Human Ovaries

Purinergic signalling has been proposed as an intraovarian regulatory mechanism. Of the receptors responsible for purinergic transmission, the P2X7 receptor is an ATP-gated cationic channel that displays a broad spectrum of cellular functions ranging from apoptosis to cell proliferation and tumourigenesis. In the present study, we investigated the functional expression of P2X7 receptors in ovarian surface epithelium (OSE). P2X7 protein was detected in the OSE layer of the mouse, both in situ and in primary cultures. In cultures, 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP) activation of P2X7 receptors increased [Ca2+]i and induced apoptosis. The functionality of the P2X7 receptor was investigated in situ by intrabursal injection of BzATP on each day of the oestrous cycle and evaluation of apoptosis 24 h using the terminal deoxyribonucleotidyl transferase-mediated dUTP–fluorescein nick end-labelling (TUNEL) assay. Maximum effects of BzATP were observed during pro-oestrus, with the effects being blocked by A438079, a specific P2X7 receptor antagonist. Immunofluorescence staining for P2X7 protein revealed more robust expression during pro-oestrus and in OSE regions behind the antral follicles, strongly supporting the notion that the differences in apoptosis can be explained by increased receptor expression, which is regulated during the oestrous cycle. Finally, P2X7 receptor expression was detected in the OSE layer of human ovaries, with receptor expression maintained in human ovaries diagnosed with cancer, as well as in the human ovarian carcinoma SKOV3 cell line.

scholarly journals Tyrosine Phosphorylation of HSP90 within the P2X7 Receptor Complex Negatively Regulates P2X7 Receptors

2003 ◽  
Vol 278 (39) ◽  
pp. 37344-37351 ◽  
Author(s):  
Elena Adinolfi ◽  
Miran Kim ◽  
Mark T. Young ◽  
Francesco Di Virgilio ◽  
Annmarie Surprenant
Keyword(s):  
Tyrosine Phosphorylation ◽  
P2x7 Receptor ◽  
Receptor Complex ◽  
P2x7 Receptors

scholarly journals Mucormycosis: An Epidemic Associated with Pandemic- A Systematic Review

2021 ◽  
Vol 5 (6) ◽  
pp. SR1-SR6
Author(s):  
Mir Tabish Syeed ◽  
Ishita Mamgain ◽  
Diksha Sharma ◽  
Ishan Trisal
Keyword(s):  
Acidic Medium ◽  
Bacterial Infections ◽  
Respiratory Illness ◽  
Treatment Modalities ◽  
Low Oxygen ◽  
Mechanical Ventilators ◽  
Co Morbidity ◽  
Wide Range ◽  
The World ◽  
General Wellbeing

Different infections have been presenting danger to mankind every once in a while and in 2019 a serious respiratory illness (COVID-19) reported in Wuhan, Hubei province of China, became a threat to general wellbeing not only in China but all the nations throughout the world. COVID-19 disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found to be associated with a wide range of opportunistic fungal and bacterial infections. Candidial and aspergillus infections leading to mucormycosis and orbital compartment syndrome have been reported to be the main co-infections in COVID-19 patients, which must be recognized and treated promptly to avoid any morbidity and mortality. Low oxygen environment, acidic medium, high glucose, decreased phagocytic activity and increased ferritin levels in addition to prolonged hospitalization with or without mechanical ventilators are considered as the main risk factors. Thus, the main aim of the article is to briefly survey and discuss about the types, causes, methods to prevent and treatment modalities of main co-morbidity of COVID 19 i.e. mucormycosis.

Current State and Prospective Trends of Black Pepper (Piper nigrum L.) Production

1986 ◽  
Vol 15 (4) ◽  
pp. 186-195 ◽  
Author(s):  
P. W. F. de Waard
Keyword(s):  
Control Measure ◽  
Supply And Demand ◽  
Black Pepper ◽  
Normal Diet ◽  
Piper Nigrum ◽  
World Production ◽  
Factors Affecting ◽  
Current State ◽  
The World ◽  
Important Constituent

Although pepper is not quantitatively a major crop – exportable world production totalling only some 132 000 tonnes annually, valued at US $162 million – it is a very important constituent of the normal diet in many parts of the world. This article reviews the factors affecting the growth of the crop and the problems of maintaining a balance between supply and demand. It argues that a major obstacle to stabilizing the industry is the lack of a satisfactory control measure for the devastating footrot disease.

Oxidative stress-induced increase of intracellular zinc in astrocytes decreases their functional expression of P2X7 receptors and engulfing activity

Metallomics ◽  
2017 ◽  
Vol 9 (12) ◽  
pp. 1839-1851 ◽  
Author(s):  
Takahiro Furuta ◽  
Ayumi Mukai ◽  
Akihiro Ohishi ◽  
Kentaro Nishida ◽  
Kazuki Nagasawa
Keyword(s):  
Oxidative Stress ◽  
Plasma Membrane ◽  
Expression Profile ◽  
P2x7 Receptor ◽  
Splice Variants ◽  
Functional Expression ◽  
P2x7 Receptors ◽  
Intracellular Zinc

Exposure of astrocytes to oxidative stress induces an increase of intracellular labile zinc and a decrease of functional expression of P2X7 receptorviaits translocation from the plasma membrane to the cytosol by altering the expression profile of P2X7 receptor and its splice variants, leading to a decrease of their engulfing activity.

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