Ectonucleotidases as bridge between the ATP and adenosine world: reflections on Geoffrey Burnstock

Abstract

Historically, mainly by the work of Robert Berne, extracellular adenosine was the first purine compound recognized as an important signaling molecule linking energy metabolism to function by acting on membrane bound receptors. Geoffrey Burnstock by his vision and endurance pioneered the idea that cells release ATP that also acts as an extracellular signaling molecule under many physiological and pathophysiological circumstances. Only later, it was appreciated that extracellular ATP and adenosine are metabolically linked by the activity of several ectoenzymes which critically determine the concentrations of these purines at their respective receptors. In this brief review, I will report some personal recollections on Geoffrey Burnstock and his impressive personality. In addition, I will give a brief overview on our present knowledge of extracellular purine metabolism and its control and will address some still open issues.

Preparation and characterization of ATP-loaded chitosan/alginate nanoparticles for therapeutic applications

“…A variety of physiological and pathophysiological circumstances cause cells to release ATP, which acts as an extracellular signaling molecule. There are several ectoenzymes involved in the metabolism of extracellular ATP and adenosine that determine their concentrations at their respective receptors [42] . An ectonucleotidase is an enzyme that metabolizes nucleotides externally oriented and expressed on the plasma membrane.…”

The role of the ATP-adenosine axis in ischemic stroke

“…Thereafter, extracellular adenosine originates mainly from parenchymal cells where it accumulates in a pO 2 -dependent manner [ 110 ]. Consequently, the gradient between extracellular and intracellular adenosine concentrations is reversed, and adenosine is released from the cells to the extracellular space [ 6 , 111 ]. Under hypoxic conditions, mitochondria consume ATP, and accumulating AMP cannot be reconverted to ATP due to the lack of oxygen and glucose.…”

“…Intracellular adenosine concentrations further rise due to the hypoxia-induced inhibition of adenosine kinase which removes adenosine by phosphorylation into AMP and represents another key enzyme for the regulation of ambient adenosine levels [ 113 – 115 ]. Given that all these cellular and enzymatic processes determine adenosine concentration, caution should be taken in extrapolating tissue adenosine levels from measurements of CD73 mRNA or protein expression only [ 111 ].…”