ArticleBritish journal of pharmacology2005
The mechanism by which ethanol inhibits rat P2X4 receptors is altered by mutation of histidine 241.
Article in British journal of pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Pharmacological differences between human and mouse P2X4 receptor explored using old and new tools.Purinergic signalling · 2024Article
- P2X4 Receptor Function in the Nervous System and Current Breakthroughs in Pharmacology.Frontiers in pharmacology · 2017Review
- 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
- Conserved extracellular cysteines differentially regulate the potentiation produced by Zn2+ in rat P2X4 receptors.European journal of pharmacology · 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
- Activation and regulation of purinergic P2X receptor channels.Pharmacological reviews · 2011Review
- Ethanol is a fast channel inhibitor of P2X4 receptors.The Journal of pharmacology and experimental therapeutics · 2011Article
- Ivermectin antagonizes ethanol inhibition in purinergic P2X4 receptors.The Journal of pharmacology and experimental therapeutics · 2010Article
- A point mutation in the ectodomain-transmembrane 2 interface eliminates the inhibitory effects of ethanol in P2X4 receptors.Journal of neurochemistry · 2010Article
- Roles of ectodomain and transmembrane regions in ethanol and agonist action in purinergic P2X2 and P2X3 receptors.Neuropharmacology · 2008Article
- Pharmacology of P2X channels.Pflugers Archiv : European journal of physiology · 2006Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
1. We investigated ethanol inhibition of the rat P2X(4) receptor and the contribution of the three histidine residues in the extracellular loop of this receptor to ethanol inhibition of receptor function, using site-directed mutagenesis and electrophysiological characterization of recombinant receptors. 2. In the wild-type receptor, 50, 200 and 500 mM ethanol increasingly shifted the ATP concentration-response curve to the right in a parallel manner, increasing the EC(50) value without affecting E(max). However, 750 or 900 mM ethanol did not produce a further increase in the EC(50) value of the ATP concentration-response curve, suggesting that this inhibition is not competitive. 3. The P2X(4) receptor mutations H140A and H286A did not significantly alter ethanol inhibition of ATP-activated current. By contrast, the mutation H241A changed the mechanism by which ethanol inhibits receptor function; viz., ethanol inhibition was not associated with an increased EC(50) value of the ATP concentration-response curve, instead, ethanol decreased the maximal response to ATP without affecting the EC(50) value of the ATP concentration-response curve. 4. Ethanol inhibition of the H241A mutant was voltage independent between -60 and +20 mV and ethanol did not alter the reversal potential of ATP-activated current. In addition, ethanol decreased the desensitization rate of the H241A-mediated current. 5. The purinoceptor antagonists, suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), did not alter the magnitude of ethanol inhibition of ATP-activated current in the H241A mutant. 6. The results suggest that ethanol inhibits the wild-type rat P2X(4) receptor by an allosteric action to increase the EC(50) value of the ATP concentration-response curve, the P2X(4) receptor mutation H241A alters the mechanism by which ethanol inhibits P2X(4) receptor function, and ethanol and PPADS or suramin appear to inhibit H241A-mutated receptors at independent sites.
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