ArticleJournal of neurochemistry2010
A point mutation in the ectodomain-transmembrane 2 interface eliminates the inhibitory effects of ethanol in P2X4 receptors.
Article in Journal of neurochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 35 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 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
- Resolving the Ionotropic P2X4 Receptor Mystery Points Towards a New Therapeutic Target for Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Residues in Transmembrane Segments of the P2X4 Receptor Contribute to Channel Function and Ethanol Sensitivity.International journal of molecular sciences · 2020Article
- Preclinical evaluation of avermectins as novel therapeutic agents for alcohol use disorders.Psychopharmacology · 2018Review
- Reduced expression of purinergic P2X4 receptors increases voluntary ethanol intake in C57BL/6J mice.Alcohol (Fayetteville, N.Y.) · 2018Article
- Ethanol differentially modulates P2X4 and P2X7 receptor activity and function in BV2 microglial cells.Neuropharmacology · 2018Article
- P2X4: A fast and sensitive purinergic receptor.Biomedical journal · 2017Review
- Preclinical development of moxidectin as a novel therapeutic for alcohol use disorder.Neuropharmacology · 2017Article
- P2X4 Receptor Function in the Nervous System and Current Breakthroughs in Pharmacology.Frontiers in pharmacology · 2017Review
- Involvement of Purinergic P2X4 Receptors in Alcohol Intake of High-Alcohol-Drinking (HAD) Rats.Alcoholism, clinical and experimental research · 2015Article
- Regulation of ATP-gated P2X channels: from redox signaling to interactions with other proteins.Antioxidants & redox signaling · 2014Review
- Contribution of P2X4 receptors to ethanol intake in male C57BL/6 mice.Neurochemical research · 2014Article
- Structural and functional properties of the rat P2X4 purinoreceptor extracellular vestibule during gating.Frontiers in cellular neuroscience · 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
- Pharmacological insights into the role of P2X4 receptors in behavioural regulation: lessons from ivermectin.The international journal of neuropsychopharmacology · 2013Article
- Multiple roles of the extracellular vestibule amino acid residues in the function of the rat P2X4 receptor.PloS one · 2013Article
- Recent advances in the discovery and preclinical testing of novel compounds for the prevention and/or treatment of alcohol use disorders.Alcoholism, clinical and experimental research · 2013Review
- Ivermectin reduces alcohol intake and preference in mice.Neuropharmacology · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
ATP-gated P2X4 receptors (P2X4R) are abundantly expressed in the CNS. However, little is known about the molecular targets for ethanol action in P2X4Rs. The current investigation tested the hypothesis that the ectodomain-transmembrane (TM) interface contains residues that are important for the action of ethanol in P2X4Rs. Wild type (WT) and mutant P2X4R were expressed in Xenopus oocytes. ATP concentration-response curves and ethanol (10-200 mM)-induced changes in ATP EC(10)-gated currents were determined using two-electrode voltage clamp (-70 mV). Alanine substitution at the ectodomain-TM1 interface (positions 50-61) resulted in minimal changes in ethanol response. On the other hand, alanine substitution at the ectodomain-TM2 interface (positions 321-337) identified two key residues (D331 and M336) that significantly reduced ethanol inhibition of ATP-gated currents without causing marked changes in ATP I(max), EC(50), or Hill's slope. Other amino acid substitutions at positions 331 and 336 significantly altered or eliminated the modulatory effects of ethanol. Linear regression analyses revealed a significant relationship between hydropathy and polarity, but not molecular volume/molecular weight of the residues at these two positions. The results support the proposed hypothesis and represent an important step toward developing ethanol-insensitive receptors for investigating the role of P2X4Rs in mediating behavioral effects of ethanol.
Indexed as
Identifiers
What OpenQuestion holds
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.