Ethanol differentially affects ATP-gated P2X and P2X receptor subtypes expressed in oocytes

Davies, Daryl L.; Kochegarov, Andrei; Kuo, Sacha T.; Kulkarni, Ashutosh A.; Woodward, John J.; King, Brian F.; Alkana, Ronald L.

doi:10.1016/j.neuropharm.2005.03.015

Cited by 71 publications

(86 citation statements)

References 37 publications

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“…Effective submaximal concentrations of agonist (EC 5-10 furthered referred to as EC 10 ) were used in the current studies. We have previously shown that the use of EC 10 can maximize the effects of ethanol and minimize receptor desensitization (Davies et al, 2002;Davies et al, 2005). Ethanol was co-applied with the agonists.…”

Section: Methodsmentioning

confidence: 99%

“…Using the Xenopus oocyte expression system in combination with the two-electrode voltage electrophysiology, we and others have demonstrated that ethanol reversibly inhibits ATP-activated function of P2X2 and P2X4Rs (Davies et al, 2002;Xiong et al, 2000). In contrast, ATP-gated currents in P2X3Rs are potentiated by ethanol (Davies et al, 2005). More recent work found that mutating a residue in the ectodomain of P2X4Rs changes the magnitude of ethanol inhibition (Xiong et al, 2005), suggesting that the ectodomain of P2XRs may be one important determinant of ethanol action on these receptors.…”

Section: Introductionmentioning

confidence: 91%

“…Xenopus oocytes were isolated and maintained as described previously (Davies et al, 2002;Davies et al, 2005). All procedures for the maintenance of Xenopus Laevis frogs and oocyte isolation were approved by The Institutional Animal Care and Use Committee of the University of Southern California.…”

Section: Isolation Of Xenopus Laevis Oocytes and Crna Injectionsmentioning

confidence: 99%

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Roles of ectodomain and transmembrane regions in ethanol and agonist action in purinergic P2X2 and P2X3 receptors

Asatryan¹,

Popova²,

Woodward³

et al. 2008

Neuropharmacology

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SUMMARYThe present work investigated sites of ethanol action in ATP-gated P2X receptors (P2XRs) using chimeric strategies that exploited the differences in ethanol response between P2X2R (inhibition) and P2X3R (potentiation). We tested ethanol (10-200mM) effects on ATP-and α,β-methylene-ATP (α,β-meATP)-induced currents in wildtype P2X2, P2X3 and chimeric P2X2/P2X3Rs expressed in Xenopus oocytes using two-electrode voltage-clamp (−70mV). Exchanging ectodomain regions of P2X2 and P2X3Rs reversed wildtype ethanol responses. Substituting back portions of the P2X2R ectodomain at TM interfaces in chimeras that contained the P2X3R ectodomain restored wildtype P2X2R-like ethanol response. Point mutations that replaced non-conserved ectodomain residues at TM interfaces of P2X3Rs with homologous P2X2R residues identified positions that reversed the direction (304) or changed the magnitude (53, 55 and 313) of ethanol response. Homologous substitutions in P2X2Rs did not significantly alter wildtype P2X2R-like ethanol responses. These findings suggest that ectodomain segments at TM interfaces play key roles in determining qualitative and quantitative responses to ethanol of P2X2 and P2X3Rs. Studies that substituted TM regions of P2X3R with respective P2X2R TMs indicate that the TM1, but not the TM2, region plays a role in determining the magnitude of ethanol response. Studies with ATP and α,β-meATP support prior indications that TM regions are important in agonist desensitization and suggest that both ectodomain and TM regions play roles in determining agonist potency and selectivity. Overall, these findings are the first to identify potential targets for ethanol in P2X2 and P2X3Rs and should provide insight into the sites of ethanol action in other P2XRs.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

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Roles of ectodomain and transmembrane regions in ethanol and agonist action in purinergic P2X2 and P2X3 receptors

Asatryan¹,

Popova²,

Woodward³

et al. 2008

Neuropharmacology

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“…EtOH inhibits the function of most P2X receptor subtypes, with some effects reported at concentrations associated with intoxication (Davies et al 2002;Li et al 1993). The P2X4 receptor appears to be the most sensitive to inhibition by EtOH, while P2X3 receptors exhibit EtOH-induced potentiation (Davies et al 2002(Davies et al , 2005. At present, the physiologic consequences of P2X inhibition are unclear.…”

Section: Ligand-gated Ion Channels and Postsynaptic Ethanol Effectsmentioning

confidence: 98%

Synaptic Effects Induced by Alcohol

Lovinger

Roberto

2010

Current Topics in Behavioral Neurosciences

117

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Ethanol (EtOH) has effects on numerous cellular molecular targets, and alterations in synaptic function are prominent among these effects. Acute exposure to EtOH activates or inhibits the function of proteins involved in synaptic transmission, while chronic exposure often produces opposing and/or compensatory/homeostatic effects on the expression, localization, and function of these proteins. Interactions between different neurotransmitters (e.g., neuropeptide effects on release of small molecule transmitters) can also influence both acute and chronic EtOH actions. Studies in intact animals indicate that the proteins affected by EtOH also play roles in the neural actions of the drug, including acute intoxication, tolerance, dependence, and the seeking and drinking of EtOH. This chapter reviews the literature describing these acute and chronic synaptic effects of EtOH and their relevance for synaptic transmission, plasticity, and behavior. KeywordsGABA; Glutamate; Monoamine; Neuropeptide; Neurotransmitter receptor; Presynaptic; Postsynaptic; Protein phosphorylation; Synaptic plasticity; Intoxication; Tolerance; Dependence Acute Ethanol ActionsEthanol (EtOH) produces intoxication through actions on the central nervous system (CNS) at concentrations ranging from low to ~100 mM (at least in non-tolerant humans and experimental animals). A number of proteins involved in synaptic transmission are altered by EtOH effects within this concentration range. The target proteins include, but are not limited to, ion channels, neurotransmitter receptors, and intracellular signaling proteins. The first section of this article will review the literature describing the most prominent acute EtOH effects on synaptic transmission in the CNS. This review is not meant to be comprehensive, but rather to cover those effects that have been observed most consistently and are thought to contribute to intoxication.

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“…Indirectly, this relationship can also occur through ionotropic ATP receptors, that has the function of specific subtypes (P2X4R and P2X2R) inhibited by ethanol (Davies et al, 2002(Davies et al, , 2005, altering the modulation of release of different substances such as GABA, glycine and glutamate (Mori et al, 2001;Papp et al, 2004).…”

Section: Ethanol and Adenosine Relation In Different Neurotransmissiomentioning

confidence: 99%

Ethanol Interference on Adenosine System

Vasconcelos¹,

Escudeiro²,

Martin³

et al. 2012

Pharmacology

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Ethanol differentially affects ATP-gated P2X and P2X receptor subtypes expressed in oocytes

Cited by 71 publications

References 37 publications

Roles of ectodomain and transmembrane regions in ethanol and agonist action in purinergic P2X2 and P2X3 receptors

Roles of ectodomain and transmembrane regions in ethanol and agonist action in purinergic P2X2 and P2X3 receptors

Synaptic Effects Induced by Alcohol

Ethanol Interference on Adenosine System

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