The effect of acidosis on adenosine release from cultured rat forebrain neurons.
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.
Zamzow
Christina R
CR
Department of Pharmacology and Therapeutics, University of Manitoba, A203-753 McDermot Avenue, Winnipeg, MB, Canada R3E 0T6.
Bose
Ratna
R
Parkinson
Fiona E
FE
D000085:Acetates / Q000494:pharmacology; D000138:Acidosis / Q000503:physiopathology*; D000241:Adenosine / Q000378:metabolism*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005452:Fluoresceins / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D008744:Methylamines / Q000494:pharmacology; D008954:Models, Biological; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D016548:Prosencephalon / Q000166:cytology*; D011687:Purines / Q000493:pharmacokinetics; D051381:Rats; D013997:Time Factors; D014316:Tritium / Q000493:pharmacokinetics
D000085:Acetates; D018690:Excitatory Amino Acid Agonists; D005452:Fluoresceins; D008744:Methylamines; D018696:Neuroprotective Agents; D011687:Purines; D014316:Tritium; C057433:2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester; D016202:N-Methylaspartate; D000584:Amiloride; C027451:methylamine; D000241:Adenosine; C039614:ethylisopropylamiloride; C030985:purine