Universität zu Köln

Suurvali, Jaanus ORCID: 0000-0003-0133-7011, Boudinot, Pierre, Kanellopoulos, Jean and Boudinot, Sirje Ruutel ORCID: 0000-0002-8758-2490 (2017). P2X4: A fast and sensitive purinergic receptor. Biomed. J., 40 (5). S. 245 - 257. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 2320-2890

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Abstract

Extracellular nucleotides have been recognized as important mediators of activation, triggering multiple responses via plasma membrane receptors known as P2 receptors. P2 receptors comprise P2X ionotropic receptors and G protein-coupled P2Y receptors. P2X receptors are expressed in many tissues, where they are involved in a number of functions including synaptic transmission, muscle contraction, platelet aggregation, inflammation, macrophage activation, differentiation and proliferation, neuropathic and inflammatory pain. P2X4 is one of the most sensitive purinergic receptors (at nanomolar ATP concentrations), about one thousand times more than the archetypal P2X7. P2X4 is widely expressed in central and peripheral neurons, in microglia, and also found in various epithelial tissues and endothelial cells. It localizes on the plasma membrane, but also in intracellular compartments. P2X4 is preferentially localized in lysosomes, where it is protected from proteolysis by its glycosylation. High ATP concentration in the lysosomes does not activate P2X4 at low pH; P2X4 gets activated by intra-lysosomal ATP only in its fully dissociated tetraanionic form, when the pH increases to 7.4. Thus, P2X4 is functioning as a Ca2_-channel after the fusion of late endosomes and lysosomes. P2X4 modulates major neurotransmitter systems and regulates alcohol-induced responses in microglia. P2X4 is one of the key receptors mediating neuropathic pain. However, injury-induced upregulation of P2X4 expression is gender dependent and plays a key role in pain difference between males and females. P2X4 is also involved in inflammation. Extracellular ATP being a pro-inflammatory molecule, P2X4 can trigger inflammation in response to high ATP release. It is therefore involved in multiple pathologies, like post-ischemic inflammation, rheumatoid arthritis, airways inflammation in asthma, neurodegenerative diseases and even metabolic syndrome. Although P2X4 remains poorly characterized, more studies are needed as it is likely to be a potential therapeutic target in these multiple pathologies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Suurvali, Jaanus UNSPECIFIED orcid.org/0000-0003-0133-7011 UNSPECIFIED Boudinot, Pierre UNSPECIFIED UNSPECIFIED UNSPECIFIED Kanellopoulos, Jean UNSPECIFIED UNSPECIFIED UNSPECIFIED Boudinot, Sirje Ruutel UNSPECIFIED orcid.org/0000-0002-8758-2490 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-216404
DOI:	10.1016/j.bj.2017.06.010
Journal or Publication Title:	Biomed. J.
Volume:	40
Number:	5
Page Range:	S. 245 - 257
Date:	2017
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	2320-2890
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language P2X(4) RECEPTORS; NEUROPATHIC PAIN; ATP RELEASE; ETHANOL INHIBITION; HUMAN MACROPHAGES; CATION CHANNELS; NERVOUS-SYSTEM; ION-CHANNEL; FEMALE MICE; MICROGLIA Multiple languages Biochemistry & Molecular Biology; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21640