Novel pathways involved in recovery of guanine nucleotides in reperfused ischaemic rat hearts and reoxygenated myocytes

Abstract

During global ischaemia for various lengths of time followed by reperfusion, the adenine and guanine nucleotide concentrations altered in parallel. Measurements of purine precursors and breakdown products suggested that GTP was resynthesised from inosine, adenosine or the adenine nucleotides in reversible ischaemia: however, the use of three different inhibitors of the key enzyme in this pathway, IMP-dehydrogenase, was entirely without effect. To eliminate the endothelial cell barrier, the experiments were repeated with anoxic/reoxygenated cardiac myocytes. The lower rate of recovery of purine nucleotide triphosphates in myocytes compared with perfused hearts would tend to confirm the important role suggested for endothelial cells in nucleoside salvage. GTP resynthesis took place after reoxygenation by some unknown pathway unaffected by the presence of large concentrations of an IMP-dehydrogenase inhibitor. The possible relationship of these findings to purinogen, the recently discovered major source of adenine nucleotides in heart, is discussed.