Recent progress on the relationship between P2X7R and breast cancer / 医学研究生学报

As the P2X receptor family has become a research hotspot in recent years, the study on P2X7 receptor has also received extensive attention. P2X7 receptor (P2X7R) is a dual-transmembrane cation-channel receptor, which is gated in vivo by adenosine triphosphate (ATP) and can be activated. Activated P2X7 receptor can produce such effects as cationic channel opening, signal pathway activation, inflammatory mediator release and cell apoptosis. It plays an important role in the development of various tumors and inflammatory diseases. Studies have shown that the abnormal expression of P2X7 receptor affects the occurrence and development of breast cancer by activating a series of signaling pathways, which is expected to become a new target for designing anti-breast cancer drugs. Other studies have shown that multiple microRNAs can promote the occurrence and development of breast cancer by regulating the expression of P2X7 receptor gene. In this review, we reviewed the recent research advances of P2X7 receptor and the relationship between breast cancer and its abnormal expression.

The effect of activation of P2X7 receptor on Ca2+ level in lateral midbrain periaqueductal gray neuron / 医学研究生学报

Objective The main intracellular signal of P2X7 receptor activation is the increasing of Ca2+, which then presents the diversity of its physiological and pathological functions through multiple intracellular signal transduction. To observe the effect of activation of P2X7 receptor on intracellular calcium（Ca2+）level in lateral midbrain periaqueductal gray (lPAG) neurons of primary cultured rat. Methods The primary cultured lPAG neurons were randomly divided into 4 groups: control group(no drug added), only for control; BzATP group(100 μmol/L); A-740003+ BzATP group(incubate with 100 nmol/L A-740003 for 10 min, then add 10 μmol/L ofBzATP); BzATP control group(add in Ca2+-free solution for 20 min, then add BzATP). The incubation solution of control group, BzATP group and A-740003+ BzATP group are DMEM/F12 medium, and the BzATP control group is Ca2+-free. The laser scanning confocal microscopy (LSCM) was used to detect : the changes of cultured neuron Ca2+ levels by different concentrations of BzATP; the effects of A-740003 and Ca2+-free medium preincubation on BzATP-induced Ca2+ level alterations in cultured neurons. Results BzATP dose-dependently increased the Ca2+ levels in cultured lPAG neurons; A-740003 and Ca2+-free medium inhibited the BzATP-induced increasing of Ca2+ level in cultured lPAG neurons. LSCM showed: The intracellular calcium fluorescence insensity(2.48±1.05) in the BzATP group was significantly higher than that in the blank control group, BzATP control group and A-740003+ BzATP group[(1.12±0.03), (1.09±0.03), (1.14±0.08)](P<0.01). Conclusion The activation of P2X7 receptor can increase the level of lPAG neurons Ca2+ , and is associated with the extracellular Ca2+ influx.

Research progress in the role of P2X receptors in oral maxillofacial pain / 口腔疾病防治

@#Oral maxillofacial pain is one of the most common symptoms that greatly influences patients′ quality of life. Infectious diseases, nerve injuries and tumors in the oromaxillofacial region can cause facial pain. P2X receptors are located in the central and peripheral nervous system. P2X receptors are non-selective cation channels that are activated by extracellular ATP and play an important role in nociceptive processing. In recent years, research into the relationship between P2X receptors and pain has become popular. Research shows that P2X receptors are expressed in the trigeminal ganglia (TG) of the primary sensory ganglion, and the effects of P2X receptors on facial pain and their related conduction mechanisms are worthy of additional research. To provide new ideas for orofacial pain prevention and treatment, this article reviews the latest progress in research regarding the role of P2X receptors in inflammatory pain, neuropathic pain, and cancer pain, among others, of the oromaxillofacial region.

Electrical Activity of the Bladder Is Attenuated by Intravesical Inhibition of P2X2/3 Receptors During Micturition in Female Rats / 대한배뇨장애요실금학회지

PURPOSE: To simultaneously monitor electrical discharges in various bladder regions and the external urethral sphincter (EUS) during voiding contractions, and to assess the functional role of myogenic modulation of the lower urinary tract (LUT) by ionotropic purinergic receptors containing the P2X3 subunit. METHODS: Female Sprague-Dawley rats were anesthetized with urethane, and implanted with a suprapubic catheter for open cystometry. Flexible microelectrodes were placed ventrally in the bladder dome, upper bladder, lower bladder, and bladder base, along with the middle section of the exposed EUS. Intravesical P2X3-containing receptors were blocked with AF-323, a specific P2X3-P2X2/3 receptor antagonist. A digital electrophysiology amplifier was used to record electrical and cystometric signals throughout the LUT. RESULTS: Electrical activity in the LUT started before effective voiding contractions. Bladder pressure and electrical waveforms showed consistent out-of-phase activity when compared with the recordings made at the EUS. This pattern was also observed during voiding contractions in the presence of AF-353, supporting the hypothesis that during bladder distension, activation of P2X3-containing receptors is required for voiding contractions. Furthermore, the inhibition of P2X3-containing receptors significantly decreased the amplitude of electrical signals in the urinary bladder, but not the base or EUS. CONCLUSIONS: Our results provide novel information about the regulation of the micturition process by P2X3-containing receptors located in the inner layers of the bladder.

Participation of Central P2X7 Receptors in CFA-induced Inflammatory Pain in the Orofacial Area of Rats

We investigated the role of central P2X receptors in inflammatory pain transmission in the orofacial area in rats. Experiments were carried out using male Sprague-Dawley rats weighing 230-280g. Complete Freund's adjuvant (CFA, 40 microL) was applied subcutaneously to the vibrissa pad to produce inflammatory pain. The intracisternal administration of iso-PPADS tetrasodium salt, a non-selective P2X receptor antagonist, A317491 sodium salt hydrate, a P2X2/3 receptor antagonist, 5-BDBD, a P2X4 receptor antagonist, or A438079 hydrochloride, a P2X7 receptor antagonist, was performed 5 days after CFA injection. Subcutaneous injections of CFA produced increases in thermal hypersensitivity. Intracisternal injections of iso-PPADS (25 microg) or A438079 (25 or 50 microg) produced significant anti-hyperalgesic effects against thermal stimuli compared to the vehicle group. A317491 or 5-BDBD did not affect the head withdrawal latency times in rats showing an inflammatory response. Subcutaneous injections of CFA resulted in the up-regulation of OX-42, a microglia marker, and GFAP, an astrocyte marker, in the medullary dorsal horn. The intracisternal administration of A438079 reduced the numbers of activated microglia and astrocytes in the medullary dorsal horn. These results suggest that a blockade of the central P2X7 receptor produces antinociceptive effects, mediated by inhibition of glial cell function in the medullary dorsal horn. These data also indicate that central P2X7 receptors are potential targets for future therapeutic approaches to inflammatory pain in the orofacial area.

Expression and function of P2X purine receptors in the enteric nervous system / 国际外科学杂志

P2X receptors are ligand gated ion channels, extracellular ATP is their natural extracellular ligand. When any of the subtypes of P2X receptors and extracellular ATP are combined, P2X channel opens, allowing cations (calcium, sodium, potassium, etc. ) pass through. Enteric nervous system is composed of the gut myenteric plexus and submucosal plexus, in both of which P2X receptors exist, mediating different effects under physiological and pathological conditions. In this paper, the enteric nervous system,P2X receptor distribution and related functions are reviewed in order to further explore the P2X receptor in the diagnosis and treatment of intestinal diseases.

Participation of Peripheral P2X Receptors in Orofacial Inflammatory Nociception in Rats

The present study investigated the role of peripheral P2X receptors in inflammatory pain transmission in the orofacial area in rats. Experiments were carried out on male Sprague-Dawley rats weighing 220 to 280 g. Formalin (5%, 50 microL) and complete Freund's adjuvant (CFA, 25 microL) was applied subcutaneously to the vibrissa pad to produce inflammatory pain. TNP-ATP, a P2X(2,2/3,4) receptor antagonist, or OX-ATP, a P2X(7) receptor antagonist, was then injected subcutaneously at 20 minutes prior to formalin injection. One of the antagonists was administered subcutaneously at three days after CFA injection. The subcutaneous injection of formalin produced a biphasic nociceptive behavioral response. Subcutaneous pretreatment with TNP-ATP (80, 160 or 240 microg) significantly suppressed the number of scratches in the second phase produced by formalin injection. The subcutaneous injection of 50 microg of OX-ATP also produced significant antinociceptive effects in the second phase. Subcutaneous injections of CFA produced increases in mechanical and thermal hypersensitivity. Both TNP-ATP (480 microg) and OX-ATP (100 microg) produced an attenuation of mechanical hypersensitivity. However, no change was observed in thermal hypersensitivity after the injection of either chemical. These results suggest that the blockade of peripheral P2X receptors is a potential therapeutic approach to the onset of inflammatory pain in the orofacial area.

Eugenol Inhibits ATP-induced P2X Currents in Trigeminal Ganglion Neurons

Eugenol is widely used in dentistry to relieve pain. We have recently demonstrated voltage-gated Na+ and Ca2+ channels as molecular targets for its analgesic effects, and hypothesized that eugenol acts on P2X3, another pain receptor expressed in trigeminal ganglion (TG), and tested the effects of eugenol by whole-cell patch clamp and Ca2+ imaging techniques. In the present study, we investigated whether eugenol would modulate 5'-triphosphate (ATP)-induced currents in rat TG neurons and P2X3-expressing human embryonic kidney (HEK) 293 cells. ATP-induced currents in TG neurons exhibited electrophysiological properties similar to those in HEK293 cells, and both ATP- and alpha,beta-meATP-induced currents in TG neurons were effectively blocked by TNP-ATP, suggesting that P2X3 mediates the majority of ATP-induced currents in TG neurons. Eugenol inhibited ATP-induced currents in both capsaicin-sensitive and capsaicin-insensitive TG neurons with similar extent, and most ATP-responsive neurons were IB4-positive. Eugenol inhibited not only Ca2+ transients evoked by alpha,beta-meATP, the selective P2X3 agonist, in capsaicin-insensitive TG neurons, but also ATP-induced currents in P2X3-expressing HEK293 cells without co-expression of transient receptor potential vanilloid 1 (TRPV1). We suggest, therefore, that eugenol inhibits P2X3 currents in a TRPV1-independent manner, which contributes to its analgesic effect.

Effect of hypoxia on the neurons expression of P2X receptors in CA1 subfield of rat hippocampus / 第三军医大学学报

Objective To investigate the expression of P2X receptors in CA1 subfield of rat hippocampus and the effect of hypoxia on the expression. Methods We set up the hypoxia animal model of high altitude and observed the expression of P2X receptors by using immunohistochemical staining before and after hypoxia. Results Immunohistochemistry showed that there were several sub-type of P2X receptors expressed in hippocampus CA1 neurons. After long term hypoxia, the expression of these receptors was increased. Conclusion there were abundant of P2X receptors expressed on the hippocampus CA1 neurons. Hypoxia affects the expression P2X receptors.

Response of P2X receptors in CA1 region of rat hippocampus to ATP and suramin / 第三军医大学学报

Objective To investigate the effects of ATP, suramin, ivermectin (IVM) and low pH value on pyramidal cells of rat hippocampus. Methods Pyramidal cells were rapidly dissociated from the hippocampus of 7-day postnatal rats by mechanical and enzymatic methods. Effects of ATP, suramin, IVM and low pH value on P2X receptor of neurons were studied by the technique of whole cell patch clamp. Results The transmembrane current was affected by ATP and suramin. There were different effects of IVM and low pH value on ATP induced current on different neurons. Conclusion There is extensive expression of P2X receptor on hippocampus pyramidal cells of rats. The expression of P2X receptors subunits are different among neurons.

Dorsal root ganglion P2X_3 receptor expression and electrophysiological characteristics in rats with neuropathic pain / 第三军医大学学报

Objective To investigate the P2X3 receptor expression and electrophysiological characteristics in dorsal root ganglion (DRG) in rat with neuropathic pain caused by chronic constriction injury of sciatic nerve (CCI) Methods P2X3 receptor expressions in L4,L5 and L6 DRG following CCI were observed by using a polyclonal antibody to label the P2X3 receptor ATP-activated currents in corresponding DRG neurons following CCI were observed by using electrophysiological technique Results A significant increase in P2X3 immunoreactivity was observed in the ipsilateral (injured) L4,L5 and L6 DRG and spinal cord on 7,14 d after CCI In small diameter neurons,a significant increase in the number of cells exhibiting a transient current to ATP was observed on 7,14 d after CCI Moreover,amplitude of these currents was increased Conclusion After CCI,the expression and function of P2X3 receptor in corresponding DRG are increased