Adenosine in rat cerebral cortex: its determination, normal values, and correlation to AMP and cyclic AMP during...

It has recently been suggested that adenosine is a metabolic coupling factor responsible for an increased cerebral blood flow during hypoxia or increased functional activity. However, tissue adenosine concentrations have been reported to increase in situations previously shown to be unassociated with changes in tissue AMP concentrations. The present experiments were undertaken to assess cerebral cortex concentrations of adenosine under normal circumstances, and to relate changes in adenosine, AMP and cyclic AMP during shortlasting ischemia. Following freezing and extraction of tissue, adenosine was measured using high pressure liquid chromatography. In paralyzed and anaesthetized (70% N2O) rats, freezing of tissue through intact skull bone gave an adenosine concentration of 0.9 +/- 0.1 mumol-kg-1 (mean +/- S.E.M.). With freezing through the exposed dura the concentration was 3 times as high with a large scatter. When special precautions were taken to avoid tissue trauma during craniotomy, the adenosine concentration was 1.1 +/- 0.1 mumol-kg-1. It is concluded that previously reported values are erroneously high. During the first 60 s of total ischemia there was a linear correlation between increase in AMP and in adenosine concentration (as well as between adenosine and cyclic AMP concentrations). It is concluded that increases in tissue adenosine concentration only occur if AMP accumulates. However, since (relative) changes in adenosine concentrations are at least twice those of AMP, analyses of adenosine may provide sensitive measures of a change in phosphorylation state.