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Ca2+signaling is fundamental for information process-ing in the peripheral nervous system,which regulates a variety of physiological activities.Ca2+signaling and calcium homeostasis are directly associated with neuropathology.Recently,studies on Ca2+signaling contribute to a deeper comprehension of the path-ogenesis of diabetic peripheral neuropathies,which provide a new research direction for the treatment of diabetic peripheralneuropathies.This review aims to highlight the relationship be-tween calcium signaling,sensory neurones and neuroglial cells in the context of diabetic peripheral neuropathies.
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Aim To study the protective effect of the naringin on chemotactic factor CX3 CL1 of human umbilical vein endothelial cells ( HUVEC) induced by high glucose. Methods The effect of different concen-trations of naringin on HUVEC cell viability was deter-mined by MTS. HUVECs were divided into 4 groups:① control group, ② high glucose group, ③ naringin group and④high glucose treated with naringin group. After treatment for 5 days, the concentration of nitric oxide ( NO ) in the culture medium was measured by nitrate reductase; intracellular reactive oxygen species ( ROS) was analyzed with fluorescence probe; the ex-pressions of CX3 CL1 mRNA and protein were deter-mined by the reverse transcription PCR ( RT-PCR ) and Western blot ( WB ) . Results NO content in the culture medium of high glucose group was markedly de-creased, which could be increased by naringin. Com-pared with the control group, intracellular ROS in the high glucose group was drastically elevated, but narin-gin decreased the elevated ROS induced by high glu-cose. The results of RT-PCR and WB showed that nar-ingin could downregulate the increased expressions of CX3CL1 mRNA and protein induced by high glucose. Conclusion Naringin has protective effect on the in-jury of the HUVEC induced by high glucose, which is associated with reducing the expression of CX3 CL1 and the antioxidative and anti-inflammatory action.
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Objective To investigate the role of P2X7 receptor in learning and memory dysfunction induced by HIV-1 enveloped protein gp120 in rats. Methods The imitating HIV-1 associated dementia (HAD) animal models were established by intracerebroventricular (ICV) infusion of gp120 in rats. The effect of gp120 on the learning and memory dysfunction in rats was evaluated by Morris water maze (MWM) test. The role of P2X7 receptor (P2X7R) was studied by Western blot and PCR assay. Results The ICV infusion of gp120 for 3 days in rats could imitated the HAD animal model. Results of MWM test showed that the rats in the model group had longer escape latencies and errors compared with those in the control group (P < 0.01); Results of Western blot and PCR assay showed that the expressions of P2X7R and P2X7 mRNA in hippocampus of rats in the model group were significantly increased (P < 0.01). Conclusions The ICV infusion of gp120 in rats could imitate the HIV-1 associated dementia (HAD) animal models, and P2X7R may be involved in the pathophysiological process of learning and memory dysfunction caused by gp120.
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Aim To study the effect of oxymatrine (OMT)on protecting human umbilical vein endothelial cells (HUVECs)from toxicity induced by high glucose in vitro.Methods The HUVECs were cultured with medium containing different concentrations of glucose or OMT. The cells were randomly divided into 6 groups:5.5 mmol·L -1 control group(Control),22.2 mmol·L -1 high glucose (22.2 mmol·L -1 ),44.4 mmol·L -1 high glucose (44.4 mmol·L -1 ),control+OMT(control +OMT),22.2 mmol·L -1 high glu-cose +OMT(22.2 mmol·L -1 +OMT),44.4 mmol ·L -1 high glucose +OMT (44.4 mmol · L -1 +OMT).The protective effect of oxymatrine was as-sessed by MTS assays.The expression of A2B in HU-VECs was detected by Real-time quantitative PCR (qPCR)and Western Blot methods.Results The glucose was shown to have caused cytotoxicity in HU-VECs.Oxymatrine (3 μmol·L -1 )was found to have protected HUVECs from glucose toxicity effectively, and reduced the expression of A2B significantly.Con-clusion Oxymatrine can obviously protect HUVECs from cytotoxicity induced by high glucose and the effect is performed partly by decreasing A2B expression.
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Gap junctions are specialized transmembrane channels that enable the direct exchange of materials and transfer chemical or electrical signaling between adjacent cells, thus maintaining cellular homeostasis. In the nervous system, gap junction chan-nels not only mediate intercellular coupling between neurons and between glial cells, but also can be involved in secondary dam-age under pathological conditions. Recently, some studies have shown that gap junctions play an important role in neuropathic pain caused by nervous system damage. Research on the role of gap junctions in neuropathic pain can contribute to a deeper un-derstanding of the pathogenesis of neuropathic pain, providing a new research direction for the treatment of neuropathic pain.
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P2 receptors activated by purine and pyrimidine nucleotides are divided into two subclasses:P2Y receptors which are G-protein coupled and P2X receptors which are ligand-gated ion channels.The expression of specific P2X and P2Y receptor subtypes in skeletal muscle cells has been demonstrated.Purinergic signaling plays an important role in muscle regeneration of muscular dystrophy,and is involved in skeletal muscle diseases such as muscular dystrophy,tendon inflammation and epilepsy,and provides the possibility of new therapeutic strategies for the treatment of muscle diseases.
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P2 receptors are divided into two subclasses:P2X receptors which are ligand-gated ion channels and P2Y receptors which are G-protein coupled.Several kinds of P2X and P2Y receptor subtypes express in vascular endothelial cells and vascular smooth muscle cells.Purinergic signalling plays an important role in vascular diseases such as atherosclerosis,cerebral vessels ageing and blood vessel remodeling.So this signalling pathway may provide a new target to treat vascular diseases.
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ATP(adenosine 5′-triphophate)is a kind of purine involved in neural transmission and regulation.With the in-depth studying about purine and pyrimidine receptor subfamilies,ATP and its receptor will become a variety of potential drug targets of disease control.The application of resonance energy transfer technology,systematic evolution of ligands by exponential enrichment in vitro and small interfering RNA technology in vivo not only expand the perspective of purinergic signaling research,but also promote their progress in disease prevention and drug screening.
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Purinergic receptors are divided into P1(adenosine)and P2(ATP)receptors.P2 receptor are divided into two subtypes,namely P2X(ligand-gated ion channels)and P2Y(G-protein coupled)receptors.Several kinds of purinoceptor subtypes have been expressed in endocrine pancreas and participate in regulating the secretion of insulin.Purinoceptor and ligand are correlated with pathogenesis of diabetes mellitus and complications and make it possible to provide a new target to treat diabetes mellitus and complications.
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Neuropathic pain is the clinically common disease and does great harm to physical and mental health.Because its pathogenesis is still unclear and there aren′t effective therapeutic tools and the course of chronic pain lasts a long time,the study of neuropathic pain has become the hot spot and the focal point of pain research area.This article reviews various kinds of animal models of neuropathic pain,which can repeat neuropathic pain symptoms of mankind and may be effective ways to make research.By acting on P2X receptors,ATP is the signal of an important transmitting pain.By utilizing animal models of neuropathic pain,it shows that P2X receptors have an important role in the formation,transmission and regulation of pain and may be a new target of neuropathic pain therapy.
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Aim To explore the modulaory effect of tetramethylpyrazine(TMP) on the responses mediated by P2X receptors.Methods Whole-cell patch-clamp technique was used to study the effects of TMP on P2X receptor agonists-activated currents in freshly isolated rat dorsal root ganglion(DRG) neurons.Results Extracellular application of ATP of 1 to 1000 ?mol?L~(-1) activated currents in DRG neurons(n=102).The ATP-activated currents showed rapid desensitization or slow desensitization.Preapplication of TMP(0.1～10 mmol?L~(-1))markedly inhibited ATP(100 ?mol?L~(1))-activated currents in the majority of the neurons examined(89.2%,91/102).TMP(1 mmol?L~(-1)) reduced ?,?-meATP(10 ?mol?L~(-1))-activated currents.TMP(1 mmol? L~(-1)) shifted the concentration-response curve of I_(ATP) downward markedly.TMP(1 mmol?L~(-1)) did not alter the reversal potential(0 mV) of ATP-activated currents.TMP(1 mmol?L~(-1)) significantly inhibited ATP(100 ?mol?L~(-1))-activated currents potentiated by PGE_2(100 ?mol?L~(-1))or SP(0.1 ?mol?L~(-1)).Intracellular application of 10 ?mol?L~(-1) H89(which is an inhibitor of PKA) reduced the inhibitory effect of TMP on ATP(100 ?mol?L~(-1))-activated currents.Conclusion The mechanism of TMP action may be the allosteric regulation via acting on PKA system and the large extracellular region of ATP receptor-ion channel complex(P2X receptors) to affect P2X receptor agonists-activated currents in rat DRG neurons.
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Objective To observe the effects of tetramethylpyrazine (TMP) on acute nociception in rat hindpaw induced by purine 2X (P2X) receptor agonists, such as adenosine triphosphate (ATP) and ?, ?-meATP, prostaglandin E 2 (PGE 2), and substance P (SP). Methods The effects of TMP administered intraplantarlly on the acute nociception induced by P2X receptor agonists, PGE 2, or SP in the rat hindpaw were investigated by the method of the behavioral study. Results TMP (10 mmol/L) significantly depressed the acute nociception induced by ATP (1 ?mol/L) or ?, ?-meATP (0.6 ?mol/L) in the rat hindpaw. TMP (10 mmol/L) could inhibit the acute nociception induced by PGE 2 (5 ?mol/L) or ?, ?-meATP (0.2 ?mol/L) coinjected with PGE 2 (5 ?mol/L). TMP (10 mmol/L) could not affect the acute nociception induced by ?, ?-meATP (0.2 ?mol/L) coinjected with SP (10 ?mol/L). TMP could not obviously affect the inflammatory edema in rat hindpaw induced by the local administration of PGE 2, SP, or ?, ?-meATP coinjected with PGE 2 or SP individually. Conclusion The antinociceptive effects of TMP may mainly be associated with inhibiting the transmission of nociceptive information mediated by P2X receptor activation.
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AIM To study the modulation of AlCl 3 on GABA activated currents in isolated rat dorsal root ganglion (DRG) neurons. METHODS Using whole cell patch clamp technique to investigate the effects of AlCl 3 on GABA activated currents in isolated rat DRG neurons. RESULTS The majority of the neurons examined(46/58) were sensitive to GABA in the concentration range from 1 to 1 000 ?mol?L -1 . In the 46 GABA sensitive cells, responses induced by AlCl 3 manifested three types: (1) outward current(3/46); (2) inward current(5/46) and (3) no detectable response(38/46). As compared with GABA activated current, the amplitude of AlCl 3 activated current was smaller. Preapplication with low concentrations of AlCl 3 (≤100 ?mol?L -1 ), the GABA activated current in majority of the cells(32/38) was potentiated, which was dose dependent, the current in a few cells(4/38) was inhibited, while the remaining two(2/38) showed no effect. At higher concentration( 1 000 ?mol?L -1 ), AlCl 3 inhibited the GABA activated current( n =8). It was found that AlCl 3 potentiated both the peak value of and the steady state value of GABA activated currents. CONCLUSION AlCl 3 can modulate the function of GABA A receptors.
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Extracellular purine and pyrimidine nucleotides produce the biologic effects involved in activating P2 receptors.P2 receptors are divided P2X and P2Y receptor subtypes.There is molecular and functional evidence for widespread expression of P2X and P2Y receptor subtypes in osteoblasts,osteoclasts and cartilage cells of the skeletal system.Working through P2 receptors,ATP and other nucleotides released into the bone microenvironment regulate formation and activity of bone and cartilage,including development,growth,turnover and repair of biological functions.The release of nucleotides is increased under inflammatory conditions,and localized ATP release could stimulate formation and activation of osteoclasts.Abnormalities of bone remodelling can produce a variety of skeletal disorders.P2 receptors play an important role in the inflammatory disease of bone.
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Aim To investigate effects of tetramethylpyrazine (TMP) on neuropathic pain induced by P2X_3 receptor. Methods Chronic constriction injury (CCI) model was adopted. Mechanical withdrawal threshold and thermal withdrawal latency were measured and P2X_3 immunoreactivity in L_4/L_5 spinal cord was detected by immunohistochemistry. Results At day 14 after operation, the mechanical withdrawal threshold and thermal withdrawal latency in group Ⅴ(CCI group) were lower than those in groupⅠ(NS group),Ⅱ(TMP group),Ⅲ(sham group) and Ⅳ (CCI+ TMP group)(P0.05). The expression of P2X_3 receptor in L_4/L_5 spinal cord of group Ⅳ was lower than that of group Ⅴ (P