Abstract
During cerebral ischemia, dysregulated glutamate release activates N-methyl-d-aspartate (NMDA) receptors which promotes excitotoxicity and intracellular acidosis. Ischemia also induces cellular adenosine (ADO) release, which activates ADO receptors and reduces neuronal injury. The aim of this research was to determine if decreasing intracellular pH (pH(i)) enhances ADO release from neurons. Rat forebrain neurons were incubated with NMDA, acetate, propionate, 5-(N)-ethyl-N-isopropyl amiloride (EIPA) or low pH buffer. pH(i) was determined with the fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM) and cellular release of ADO was assayed. NMDA decreased pH(i) and increased ADO release from neurons. Acetate and propionate decreased pH(i) and evoked ADO release from neurons. EIPA, an inhibitor of sodium hydrogen exchanger 1 (NHE1), enhanced the acidosis in neurons but did not enhance ADO release. Decreasing extracellular pH (pH(e)) to 6.8 or 6.45 significantly decreased pH(i) in neurons, but was not consistently associated with increased ADO release. The main finding of this study was that acidosis per se did not enhance ADO release from neurons.
References
Jul 1, 1992·British Journal of Pharmacology·Y ChenT W Stone
Dec 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·A M ParadisoT E Machen
Jan 1, 1983·The Journal of Membrane Biology·W F Boron
Jul 17, 1998·Life Sciences·M YamamotoT Hayakawa
Mar 14, 2000·The Journal of Physiology·B ChengH J Ballard
Sep 13, 2000·Life Sciences·F M Mo, H J Ballard
Dec 9, 2000·Naunyn-Schmiedeberg's Archives of Pharmacology·H Zimmermann
Mar 20, 2002·Neurochemistry International·J W Phillis, M H O'Regan
Oct 18, 2002·Neuropharmacology·F E ParkinsonJ D Geiger
Oct 22, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Bernard A CoertFredric B Meyer
Apr 3, 2003·The European Journal of Neuroscience·Yin LuPaul A Rosenberg
Jul 3, 2003·Pflügers Archiv : European journal of physiology·Stephen A BaldwinJames D Young
Mar 11, 2004·Journal of Neurochemistry·Fiona E Parkinson, Wei Xiong
Sep 17, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hong LuCurtis Klaassen
Apr 15, 2005·Neurological Research·Susan A Masino, Christopher G Dulla
Apr 15, 2005·Neurological Research·Fiona E ParkinsonChristina R Zamzow
Dec 21, 2005·Neuron·Chris G DullaSusan A Masino
Citations
Jan 7, 2010·Canadian Journal of Physiology and Pharmacology·Christina R ZamzowFiona E Parkinson
Jan 17, 2013·Neurochemistry International·Dhaval P BhattThad A Rosenberger
Jul 16, 2008·Journal of Neuroscience Research·Christina R ZamzowFiona E Parkinson
May 15, 2008·Journal of Neuroscience Research·Christina R ZamzowFiona E Parkinson
Oct 13, 2010·Movement Disorders : Official Journal of the Movement Disorder Society·Tiffany L YoungJerri D Edwards