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.

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.

HIV-related sensory neuropathy ( HIV-SN) mainly contains the HIV infection-related distal sensory polyneuropa-thy (DSP) and antiretroviral toxic neuropathies (ATN).HIV-DSP is associated with proinflammatory cytokines , chemokines, ros and which is induced by gp 120;and HIV-ATN may be related to mitochondrial toxicity which is induced by the application of anti retroviral drugs, such as ddC, and similar as the molecular mechanism of HIV-DSP, this means that the current conventional method for the treatment of neuropathic pain in AIDS may further aggravate the neuropathic pain of the patient .Therefore, developing the study on the neurochemical and pharmacological mechanisms of HIV-related neuropathic pain will provide novel targets for the new effective drugs .

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.

The P2X7 receptor (P2X7 R)is a nonselective cation channel activated by extracellular ATP,and it may trigger the se-cretion of several proinflammatory substances,such as IL-1β, IL-18,TNF-α,and nitric oxide.Several preclinical studies have demonstrated that this receptor participates in inflammation and pain mechanisms,and compounds that modulate the function of this receptor show potential as new anti-inflammatory medicines. Therefore,P2X7 receptors play particularly important physiologi-cal roles and have potential clinical application in inflammation and pain,which proves it a therapeutic target for pain manage-ment.

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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.

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.

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