Bile acids inhibit human purinergic receptor P2X4 in a heterologous expression system

Ilyaskin, Alexandr V.; Sure, Florian; Nesterov, Viatcheslav; Korbmacher, Christoph

doi:10.1085/jgp.201812291

Cited by 9 publications

(15 citation statements)

References 46 publications

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“…The released ATP is thought to inhibit ENaC in principal cells in an autocrine/paracrine manner via P2Y 2 -dependent purinergic signaling causing a rise in intracellular Ca 2+ . However, endogenous expression of purinergic receptors, and hence the responsiveness to extracellular ATP, is negligible in X. laevis oocytes ( 76 , 77 ). Moreover, it has been reported that application of ATP does not inhibit ENaC-mediated currents in the oocyte expression system ( 78 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the epithelial sodium channel (ENaC) by connexin 30 involves stimulation of clathrin-mediated endocytosis

Ilyaskin

Korbmacher

Diakov

2021

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Inhibition of the epithelial sodium channel (ENaC) by connexin 30 involves stimulation of clathrin-mediated endocytosis

Ilyaskin

Korbmacher

Diakov

2021

Journal of Biological Chemistry

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“…The PIPs bind to positively charged amino acids in the cytosolic C-terminal domain and inhibit P2X receptormediated currents. The P2X4 receptors, and to some extent the P2X2 receptors, are inhibited by high ethanol concentrations ($100 mM) (Ilyaskin, Sure, Nesterov, Haerteis, & Korbmacher, 2019;Müller, 2015;Sivcev et al, 2019). F I G U R E 1 Selected P2X receptor agonists, nucleotide-derived antagonists, and positive allosteric modulators…”

Section: P2x Receptor Agonistsmentioning

confidence: 99%

Update of P2X receptor properties and their pharmacology: IUPHAR Review 30

Illéš

Müller

Jacobson

et al. 2020

British J Pharmacology

221

202

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The known seven mammalian receptor (R) subunits (P2X1-7) form cationic channels gated by ATP. Three subunits compose a receptor-channel. Each subunit is a polypeptide consisting of two transmembrane regions (TM1, TM2), intracellular Nand C-termini, and a bulky extracellular loop. Crystallization allowed the identification of the 3D-structure and gating cycle of P2XRs. The agonist binding pocket is located at the intersection of two neighboring subunits. In addition to the mammalian P2XRs their primitive ligand-gated counterparts with little structural similarity have also been cloned. Selective agonists for P2XR subtypes are not available, but medicinal chemistry supplied a range of subtype selective antagonists, as well as positive and negative allosteric modulators. Knockout mice and selective antagonists helped to identify pathological functions due to defective P2XRs, such as male infertility (P2X1), hearing loss (P2X2), pain/cough (P2X3), neuropathic pain (P2X4), inflammatory bone loss (P2X5), and faulty immune reactions (P2X7).

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“…Finally, channels of the ENaC/DEG family share a surprising similarity in structure with purinoreceptor P2X channels: trimeric channels with two transmembrane segments and a large extracellular domain [83]. P2X channels have been excluded from this review as they do not belong to the ENaC/DEG family, nevertheless exploring proteins with similar structure and similar function can lead to new perspectives.…”

Section: Perspectivesmentioning

confidence: 99%

Ion Selectivity in the ENaC/DEG Family: A Systematic Review with Supporting Analysis

Vallée

Howlin

Lewis

2021

IJMS

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The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide variety of animal species. Despite their differences, they share a high homology in the pore region in which the ion discrimination takes place. Although ion selectivity has been studied for decades, the mechanisms underlying this selectivity for trimeric channels, and particularly for the ENaC/DEG family, are still poorly understood. This systematic review follows PRISMA guidelines and aims to determine the main components that govern ion selectivity in the ENaC/DEG family. In total, 27 papers from three online databases were included according to specific exclusion and inclusion criteria. It was found that the G/SxS selectivity filter (glycine/serine, non-conserved residue, serine) and other well conserved residues play a crucial role in ion selectivity. Depending on the ion type, residues with different properties are involved in ion permeability. For lithium against sodium, aromatic residues upstream of the selectivity filter seem to be important, whereas for sodium against potassium, negatively charged residues downstream of the selectivity filter seem to be important. This review provides new perspectives for further studies to unravel the mechanisms of ion selectivity.

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Bile acids inhibit human purinergic receptor P2X4 in a heterologous expression system

Cited by 9 publications

References 46 publications

Inhibition of the epithelial sodium channel (ENaC) by connexin 30 involves stimulation of clathrin-mediated endocytosis

Inhibition of the epithelial sodium channel (ENaC) by connexin 30 involves stimulation of clathrin-mediated endocytosis

Update of P2X receptor properties and their pharmacology: IUPHAR Review 30

Ion Selectivity in the ENaC/DEG Family: A Systematic Review with Supporting Analysis

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