Regulation of extracellular adenosine in rat hippocampal slices is temperature dependent: role of adenosine transporters.
While a great deal is known about stimuli that can induce the release of adenosine from brain tissue, relatively little is known about the regulation of the basal extracellular concentration of adenosine that is present in the absence of stimulation. Under normal conditions, enough adenosine is present to tonically activate a significant portion of the high-affinity adenosine A1 receptors. The present experiments demonstrated that the estimated basal concentration of extracellular adenosine in rat hippocampal slices maintained at 21 degrees C (430 nM) is approximately twice that at 32 degrees C (220 nM). The sensitivity of presynaptic modulatory adenosine A1 receptors was not significantly different at 21 degrees C or at 32 degrees C. Slices maintained at 21 degrees C also showed a reduced ability to inactivate extracellular adenosine, which reflects a reduction in adenosine transport across cell membranes. This effect appears to be primarily due to a reduction in the function of the equilibrative, dipyridamole-sensitive (ei) adenosine transporter; the nitrobenzylthioinosine-sensitive equilibrative transporter (es transporter) appears to be relatively less affected by temperature than is the ei transporter. These experiments demonstrate that extracellular concentrations of adenosine in the brain are sensitive to temperature, and suggest that some of the neurological effects of hypothermia might be mediated via increased concentrations of adenosine in the extracellular space.
Dunwiddie
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Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
Diao
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D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D004176:Dipyridamole / Q000494:pharmacology; D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology
D002352:Carrier Proteins; D033721:Equilibrative Nucleoside Transporter 1; D033722:Equilibrative-Nucleoside Transporter 2; D008565:Membrane Proteins; C438652:Slc29a1 protein, rat; C438655:Slc29a2 protein, rat; D019830:Adenosine-5'-(N-ethylcarboxamide); D013868:Thioinosine; D004176:Dipyridamole; D000243:Adenosine Deaminase; C001789:4-nitrobenzylthioinosine; D000241:Adenosine