Masino S A, Latini S, Bordoni F, Pedata F, Dunwiddie T V
Department of Pharmacology and Neuroscience Program, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Synapse. 2001 Jul;41(1):58-64. doi: 10.1002/syn.1060.
Previous studies have demonstrated that when the temperature of hippocampal brain slices is increased, there is a corresponding depression of synaptic potentials mediated by an increased activation of presynaptic adenosine A(1) receptors. The present experiments demonstrate that when the temperature of hippocampal slices is raised from 32.5 degrees C to either 38.5 degrees C or 40.0 degrees C there is a marked, temperature-dependent increase in the efflux of endogenous adenosine and a corresponding decrease in excitatory synaptic responses. The increase in efflux is rapidly reversible on lowering the slice temperature and the temperature-induced efflux is repeatable. Control experiments suggest that this increased efflux of adenosine is not the result of hypoxia or ischemia secondary to a temperature-induced increase in the metabolic rate of the slice. The increase in adenosine efflux was not accompanied by any significant change in the ATP levels in the brain slice, whereas a hypoxic stimulus sufficient to produce a comparable depression of excitatory transmission produced an approximately 75% decrease in ATP levels. These experiments indicate that changes in brain slice temperature can alter purine metabolism in such a way as to increase the adenosine concentration in the extracellular space, as well as adenosine efflux from hippocampal slices, in the absence of significant changes in ATP levels.
以往的研究表明，当海马脑片温度升高时，由突触前腺苷A(1)受体激活增加介导的突触电位会相应降低。本实验表明，当海马脑片温度从32.5摄氏度升至38.5摄氏度或40.0摄氏度时，内源性腺苷的流出量会显著增加，且呈温度依赖性，同时兴奋性突触反应相应减少。降低脑片温度时，流出量的增加可迅速逆转，且温度诱导的流出可重复。对照实验表明，腺苷流出量的增加并非温度诱导脑片代谢率升高继发的缺氧或缺血所致。腺苷流出量的增加并未伴随脑片ATP水平的任何显著变化，而足以产生类似兴奋性传递抑制的缺氧刺激则使ATP水平降低了约75%。这些实验表明，在ATP水平无显著变化的情况下，脑片温度的改变可通过改变嘌呤代谢，增加细胞外空间腺苷浓度以及海马脑片腺苷流出量。
