ArticleNeuropharmacology2008
Roles of ectodomain and transmembrane regions in ethanol and agonist action in purinergic P2X2 and P2X3 receptors.
Article in Neuropharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- A Pilot Study of the Safety and Initial Efficacy of Ivermectin for the Treatment of Alcohol Use Disorder.Alcoholism, clinical and experimental research · 2016Trial
- A Novel Dual Drug Approach That Combines Ivermectin and Dihydromyricetin (DHM) to Reduce Alcohol Drinking and Preference in Mice.Molecules (Basel, Switzerland) · 2021Article
- A novel pharmacotherapy approach using P-glycoprotein (PGP/ABCB1) efflux inhibitor combined with ivermectin to reduce alcohol drinking and preference in mice.Alcohol (Fayetteville, N.Y.) · 2020Article
- Reduced expression of purinergic P2X4 receptors increases voluntary ethanol intake in C57BL/6J mice.Alcohol (Fayetteville, N.Y.) · 2018Article
- Preclinical development of moxidectin as a novel therapeutic for alcohol use disorder.Neuropharmacology · 2017Article
- Involvement of Purinergic P2X4 Receptors in Alcohol Intake of High-Alcohol-Drinking (HAD) Rats.Alcoholism, clinical and experimental research · 2015Article
- Contribution of P2X4 receptors to ethanol intake in male C57BL/6 mice.Neurochemical research · 2014Article
- P2X4 receptors (P2X4Rs) represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders.Frontiers in neuroscience · 2014Review
- Tryptophan 46 is a site for ethanol and ivermectin action in P2X4 receptors.Purinergic signalling · 2013Article
- Activation and regulation of purinergic P2X receptor channels.Pharmacological reviews · 2011Review
- Implication of the purinergic system in alcohol use disorders.Alcoholism, clinical and experimental research · 2011Review
- Ethanol is a fast channel inhibitor of P2X4 receptors.The Journal of pharmacology and experimental therapeutics · 2011Article
- Allosteric modulation of ATP-gated P2X receptor channels.Reviews in the neurosciences · 2011Review
- Ivermectin antagonizes ethanol inhibition in purinergic P2X4 receptors.The Journal of pharmacology and experimental therapeutics · 2010Article
- Molecular targets and mechanisms for ethanol action in glycine receptors.Pharmacology & therapeutics · 2010Review
- A point mutation in the ectodomain-transmembrane 2 interface eliminates the inhibitory effects of ethanol in P2X4 receptors.Journal of neurochemistry · 2010Article
- Loop 2 structure in glycine and GABA(A) receptors plays a key role in determining ethanol sensitivity.The Journal of biological chemistry · 2009Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The 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 alpha,beta-methylene-ATP (alpha,beta-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 alpha,beta-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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.