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 ad enosine from brain tissue, relatively little is known about the regulation of the basal extracellular concentration of adenosine that is present in th e absence of stimulation. Under normal conditions, enough adenosine is pres ent to tonically activate a significant portion of the high-affinity adenos ine A(1) receptors. The present experiments demonstrated that the estimated basal concentration of extracellular adenosine in rat hippocampal slices m aintained at 21 degrees C (430 nM) is approximately twice that at 32 degree s C (220 nM). The sensitivity of presynaptic modulatory adenosine Al recept ors was not significantly different at 21 degrees C or at 32 degrees C. Sli ces 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 reducti on in the function of the equilibrative, dipyridamole-sensitive (ei) adenos ine transporter; the nitrobenzyltkioinosine-sensitive equilibrative transpo rter (es transporter) appears to be relatively less affected by temperature than is the ei transporter. These experiments demonstrate that extracellul ar concentrations of adenosine in the brain are sensitive to temperature, a nd suggest that some of the neurological effects of hypothermia might be me diated via increased concentrations of adenosine in the extracellular space . Published by Elsevier Science Ltd.