Extracellular nucleotides in exercise: possible effect on brain metabolism

ATP and other nucleotide derivatives have potent extracellular effects. Sensitive and rapid techniques of ATP detection have shown that ATP is (1) released from active skeletal muscle in vasodilator quantities and (2) released from isolated heart cells in response to hypoxia. Release of nucleotides from active brain tissue has also been demonstrated (Pull and McIlwain, 1972). It is calculated that active cerebral tissue releases sufficient ATP to satisfy local vasodilator requirements in the brain. Intracarotid infusions of ATP have the effect of stimulating oxygen uptake in brain tissue and profoundly increasing the cerebral blood flow. It is not understood how the ATP can exert these effects beyond the blood : brain barrier. Since exercising skeletal muscle releases ATP and other nucleotide derivatives into the circulation, it is postulated that the metabolism of the brain can be significantly affected in exercise. These data, together with the studies by Pritchard et al. (1975) on uptake and supply of purine compounds by the liver, prompt the suggestion that there exists a system of "metabolic communication" in the body mediated by circulating purine compounds.