ArticlePflugers Archiv : European journal of physiology2008
Identification of P2X(4) receptor transmembrane residues contributing to channel gating and interaction with ivermectin.
Article in Pflugers Archiv : European journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Cell Type-Specific Expression of Purinergic P2X Receptors in the Hypothalamus.International journal of molecular sciences · 2025Review
- Human P2X4 receptor gating is modulated by a stable cytoplasmic cap and a unique allosteric pocket.Science advances · 2025Article
- Residues in Transmembrane Segments of the P2X4 Receptor Contribute to Channel Function and Ethanol Sensitivity.International journal of molecular sciences · 2020Article
- Bile acids inhibit human purinergic receptor P2X4 in a heterologous expression system.The Journal of general physiology · 2019Article
- Article
- Preclinical evaluation of avermectins as novel therapeutic agents for alcohol use disorders.Psychopharmacology · 2018Review
- Ivermectin and its target molecules: shared and unique modulation mechanisms of ion channels and receptors by ivermectin.The Journal of physiology · 2018Review
- Ivermectin activates GIRK channels in a PIPThe Journal of physiology · 2017Article
- P2X4 ReceptorFrontiers in pharmacology · 2017Article
- Role of purinergic P2X4 receptors in regulating striatal dopamine homeostasis and dependent behaviors.Journal of neurochemistry · 2016Article
- Roles of the lateral fenestration residues of the P2X₄ receptor that contribute to the channel function and the deactivation effect of ivermectin.Purinergic signalling · 2015Article
- Allosteric regulation of the P2X4 receptor channel pore dilation.Pflugers Archiv : European journal of physiology · 2015Article
- Imaging P2X4 receptor subcellular distribution, trafficking, and regulation using P2X4-pHluorin.The Journal of general physiology · 2014Article
- Article
- 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
- P2X receptors as drug targets.Molecular pharmacology · 2013Review
- Review
- Size matters in activation/inhibition of ligand-gated ion channels.Trends in pharmacological sciences · 2012Review
- Molecular and functional properties of P2X receptors--recent progress and persisting challenges.Purinergic signalling · 2012Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Ivermectin (IVM), a large macrocyclic lactone, specifically enhances P2X(4) receptor-channel function by interacting with residues of transmembrane (TM) helices in the open conformation state. In this paper, we used cysteine-scanning mutagenesis of rat P2X(4)-TMs to identify and map residues of potential importance for channel gating and interaction with IVM. The receptor function was unchanged by mutations in 29 different residues, and among them, the IVM effects were altered in Gln(36), Leu(40), Val(43), Val(47), Trp(50), Asn(338), Gly(342), Leu(346), Ala(349), and Ile(356) mutants. The substitution-sensitive Arg(33) and Cys(353) mutants could also be considered as IVM-sensitive hits. The pattern of these 12 residues was consistent with helical topology of both TMs, with every third or fourth amino acid affected by substitution. These predominantly hydrophobic-nonpolar residues are also present in the IVM-sensitive Schistosoma mansoni P2X subunit. They lie on the same side of their helices and could face lipids in the open conformation state and provide the binding pocket for IVM. In contrast, the IVM-independent hits Met(31), Tyr(42), Gly(45), Val(49), Gly(340), Leu(343), Ala(344), Gly(347), Thr(350), Asp(354), and Val(357) map on the opposite side of their helices, probably facing the pore of receptor or protein and playing important roles in gating.
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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.