Kinetics of antagonist actions at rat P2X2/3 heteromeric receptors

British Journal of Pharmacology
Valeria SpeltaR A North

Abstract

1. Currents through heteromeric P2X(2/3) receptors were evoked by applying alpha,beta-methylene-ATP to human embryonic kidney cells transfected with cDNAs encoding the P2X(2) and P2X(3) subunits. The concentration of alpha,beta-methylene-ATP were < or =30 microM because higher concentrations can activate homomeric P2X(2) receptors. The kinetics of action of three structurally unrelated antagonists were studied; these were 2', 3'-O-(2,4,6,trinitrophenyl)-ATP (TNP-ATP), pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonate (PPADS) and suramin. The association and dissociation rate constants were determined by pre-applying the antagonist for various periods prior to the co-application of agonist and antagonist, or by changing the solution from one containing only the agonist to one containing both agonist and antagonist. The high affinity of TNP-ATP for the P2X(2/3) receptor (K(D) approximately 2 nM) results from fast binding (k(+1) approximately 100 microM(-1) s(-1)) rather than slow unbinding (k(-1) approximately 0.3 s(-1)). For suramin (K(D) approximately 1 microM) the association rate constant ( approximately 1 microM(-1) s(-1)) was 100 times slower than that of TNP-ATP but the dissociation rate constant was similar (k(-1) appr...Continue Reading

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Citations

May 2, 2006·Pflügers Archiv : European journal of physiology·Joel R GeverAnthony P D W Ford
Apr 21, 2011·Pflügers Archiv : European journal of physiology·Jie ZouLin-Hua Jiang
Mar 22, 2002·British Journal of Pharmacology·Michael F Jarvis, Edward C Burgard
Jul 28, 2010·The Journal of Biological Chemistry·Wei YangLin-Hua Jiang
Jul 9, 2011·Pharmacological Reviews·Claudio CoddouStanko S Stojilkovic
Aug 5, 2008·Biochemical and Biophysical Research Communications·Rong XiaLin-Hua Jiang
Oct 18, 2005·Pharmacology & Therapeutics·Geoffrey Burnstock
Oct 29, 2003·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Jianguo G Gu
Dec 2, 2009·Molecular Pain·Geoffrey Burnstock
Jun 27, 2003·Anesthesiology·Philip M LangPeter Grafe
Oct 29, 2003·British Journal of Pharmacology·Valeria SpeltaR Alan North
Jul 2, 2003·The Journal of Physiology·R Alan North
Apr 13, 2007·Physiological Reviews·Geoffrey Burnstock
Mar 31, 2019·British Journal of Pharmacology·David RichardsSamuel J Fountain
Mar 2, 2006·Pharmacological Reviews·Geoffrey Burnstock
Dec 1, 2007·The Journal of Pharmacology and Experimental Therapeutics·Brian F King, Andrea Townsend-Nicholson
May 23, 2003·Molecular Pharmacology·Xuenong BoR Alan North
Mar 17, 2004·The Journal of Pharmacology and Experimental Therapeutics·Michael F JarvisConnie Faltynek
Sep 25, 2002·Physiological Reviews·R Alan North
Jan 24, 2012·Biochimica Et Biophysica Acta·Alberto Baroja-MazoPablo Pelegrín
Sep 2, 2003·Biochimica Et Biophysica Acta·Erik M Schwiebert, Akos Zsembery

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