ABSTRACT
Adenosine triphosphate (ATP) is well-known as a universal source of energy in living cells. Less known is that this molecule has a variety of important signaling functions: it activates a variety of specific metabotropic (P2Y) and ionotropic (P2X) receptors in neuronal and non-neuronal cell membranes. So, a wide variety of signaling functions well fits the ubiquitous presence of ATP in the tissues. Even more ubiquitous are protons. Apart from the unspecific interaction of protons with any protein, many physiological processes are affected by protons acting on specific ionotropic receptors-acid-sensing ion channels (ASICs). Both protons (acidification) and ATP are locally elevated in various pathological states. Using these fundamentally important molecules as agonists, ASICs and P2X receptors signal a variety of major brain pathologies. Here we briefly outline the physiological roles of ASICs and P2X receptors, focusing on the brain pathologies involving these receptors.
Subject(s)
Humans , Acid Sensing Ion Channels , Protons , Neurons , Brain Diseases , Adenosine Triphosphate/physiologyABSTRACT
AIM: To investigate the effects of sodium hydrosulfide ( NaHS ) , a donor of hydrogen sulfide ( H2 S) , on the membrane permeability , intracellular Ca 2+concentration ( [ Ca2+] i ) and the release of IL-1βinduced by a-denosine triphosphate (ATP) in rat microglia, and to explore the effect of H2S on ATP-P2X purinergic signaling pathway and the molecular mechanism of its neuroprotective effect .METHODS: Rat microglia in logarithmic growth phase were used in the study.The [Ca2+]i was detected by Fura-2/AM staining.Fluorescent dye YO-PRO-1 was used to observe the membrane permeability.Interleukin-1β(IL-1β) was measured by rat IL-1βELISA kits.RESULTS:The YO-PRO-1 flu-orescence intensity was obviously elevated by ATP induction in a dose -dependent manner in the rat microglia , but this effect was counteracted by NaHS pretreatment (P<0.05).[Ca2+]i rapidly increased and then decreased slowly , forming a sta-ble platform for a long time when rat microglia were treated with ATP .Ca2+spike activity induced by ATP had no change , but the platform disappeared (P<0.05) after NaHS pretreatment.The ATP and LPS together facilitated the release of IL-1β, but the phenomenon was inhibited by NaHS (P<0.05).CONCLUSION:Hydrogen sulfide may decrease the mem-brane permeability , calcium inflow and IL-1βrelease in rat microglia activated by high dose of ATP .The cytoprotection of hydrogen sulfide may be mediated by purinergic signaling pathway .
ABSTRACT
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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Objective:To compare the effects of Zn~(2+)onthe P2X receptor-mediated,ATP-induced currents in neurons separated from rat superior cervical ganglion(SCG),nodose ganglion(NG),and otic ganglion(OTG).Methods: Whole-cell patch clamp recording technique was used to study the regulatory effects of Zn~(2+) on ATP/??-me ATP-induced currents in the above 3 ganlglion neurons.Results: All SCG neurons responded to ATP with a sustained current,while no neurons responded to ??-me ATP;Zn~(2+) potentiated ATP-induced sustained currents to(1 442?34)% of the original value.All NG neurons responded to ATP and ??-me ATP with a similar sustained current;coapplication of Zn~(2+)(10 ?mol/L) potentiated their responses to(180?12)% and(262?28)%,respectively.All OTG neurons responded to both ATP and ??-me ATP with a sustained current.Coapplication of Zn~(2+)(10 ? mol/L) did not significantly potentiate the sustained currents induced by 10 ?mol/L ATP,but when ATP was at 30 ?mol/L,Zn~(2+)(10-100 ?mol/L) inhibited ATP-induced sustained currents in a dose dependent manner.If TNP-ATP(100 nmol/L) was first used to inhibit ATP-induced current to(26?2)% of the original value,Zn~(2+) at 10 ?mol/L potentiated the inhibited current to(127?9)% of its original value.Coapplication of Zn~(2+)(10 ?mol/L) potentiated ??-me ATP-induced currents to(146?5)% of the control.Zn~(2+)(300 ?mol/L) had no effect on ?_(on) and ?_(off) of ATP-and ??-me ATP-induced(30 ?mol/L) currents in OTG neurons.Conclusion:(1) Zn~(2+) is an allosteric modulator of P2X_(2) and P2X_(2/3) receptors in SCG and NG neurons and can potentiate the currents they induced.(2)The predominant receptor subtypes in OTG appear to be homomeric P2X_(2/3) and a little P2X_(2).Zn~(2+) has an inhibitory effect on the ATP-induced currents in OTG neurons,suggesting some novel members of the P2X purinoceptor exist in these neurons.