P2X7 ionotropic receptor is functionally expressed in rabbit articular chondrocytes and mediates extracellular ATP cytotoxicity

Purinergic Signalling
Hitoshi TanigawaShinji Imai

Abstract

Extracellular ATP regulates various cellular functions by engaging multiple subtypes of P2 purinergic receptors. In many cell types, the ionotropic P2X7 receptor mediates pathological events such as inflammation and cell death. However, the importance of this receptor in chondrocytes remains largely unexplored. Here, we report the functional identification of P2X7 receptor in articular chondrocytes and investigate the involvement of P2X7 receptors in ATP-induced cytotoxicity. Chondrocytes were isolated from rabbit articular cartilage, and P2X7 receptor currents were examined using the whole-cell patch-clamp technique. ATP-induced cytotoxicity was evaluated by measuring caspase-3/7 activity, lactate dehydrogenase (LDH) leakage, and prostagrandin E2 (PGE2) release using microscopic and fluorimetric/colorimetric evaluation. Extracellular ATP readily evoked a cationic current without obvious desensitization. This ATP-activated current was dose related, but required millimolar concentrations. A more potent P2X7 receptor agonist, BzATP, also activated this current but at 100-fold lower concentrations. ATP-induced currents were largely abolished by selective P2X7 antagonists, suggesting a predominant role for the P2X7 receptor. RT-PCR...Continue Reading

References

Dec 1, 1992·Arthritis and Rheumatism·L M RyanV M Kushnaryov
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Nov 19, 1997·Neuropharmacology·C VirginioA Surprenant
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·S HashimotoM Lotz
Sep 29, 1998·Arthritis and Rheumatism·S HashimotoM Lotz
Sep 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·K NotoyaJ P Pelletier
Aug 2, 2002·European Journal of Pharmacology·Rosalind Le FeuvreNancy Rothwell
Sep 6, 2002·Journal of Medicinal Chemistry·Kenneth A JacobsonMichael Williams
Sep 25, 2002·Physiological Reviews·R Alan North
Apr 14, 2004·Current Topics in Medicinal Chemistry·Geoffrey Burnstock
Nov 20, 2004·The Journal of Biological Chemistry·Mitsutoshi TsukimotoKuniaki Takagi
Dec 1, 2006·The Journal of Biological Chemistry·Nattapon PanupinthuS Jeffrey Dixon
Mar 31, 2007·Journal of Neurochemistry·Claudio Acuña-CastilloJ Pablo Huidobro-Toro
Jun 15, 2007·British Journal of Pharmacology·H JiangJ C McGiff
Oct 27, 2007·The Journal of Biological Chemistry·Dong-Jae JunKyong-Tai Kim
Dec 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Simon R J TaylorJames I Elliott
Aug 30, 2008·Experimental Physiology·Geoffrey Burnstock
Nov 6, 2008·Prostaglandins & Other Lipid Mediators·Helio Miranda Costa-JuniorPedro Muanis Persechini
Jun 30, 2009·British Journal of Pharmacology·Diana L Donnelly-RobertsMichael F Jarvis
Nov 6, 2009·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Mariana Garcia, Martin M Knight
Jan 15, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Hiroshi MiyoshiYoshiki Kudo
Jul 24, 2010·British Journal of Pharmacology·W NörenbergP Illes
Aug 17, 2010·Osteoarthritis and Cartilage·A K RosenthalL M Ryan
Feb 18, 2011·Journal of Cellular Physiology·Rebecca LewisRichard Barrett-Jolley
Apr 5, 2011·British Journal of Pharmacology·Helen J BradleyLin-Hua Jiang
Oct 9, 2012·Neuron·Baljit S Khakh, R Alan North
Oct 16, 2012·Channels·Ali MobasheriRichard Barrett-Jolley
May 22, 2013·Purinergic Signalling·Juan Pablo ReyesS Jeffrey Dixon
Oct 3, 2013·International Journal of Molecular Sciences·Kousuke KumagaiYoshitaka Matsusue
Feb 28, 2014·Frontiers in Physiology·Valery I Shestopalov, Vladlen Z Slepak
Jun 15, 2014·Pharmacological Reviews·Rachael BartlettRonald Sluyter
Oct 30, 2014·Purinergic Signalling·Geoffrey Burnstock, Jean-Marie Boeynaems

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Citations

Sep 29, 2020·Frontiers in Medicine·Paula GratalAránzazu Mediero
Jan 14, 2021·Journal of Leukocyte Biology·Shamima AkterRavi Shankar Akundi
Jan 18, 2021·European Journal of Pain : EJP·Juliana M TeixeiraJuliana T Clemente-Napimoga

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Methods Mentioned

BETA
enzymatic dissociation
transfection
Assay
PCR

Software Mentioned

Image J
Patchmaster

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