NOVEL PATHWAYS INVOLVED IN RECOVERY OF GUANINE-NUCLEOTIDES IN REPERFUSED ISCHEMIC RAT HEARTS AND REOXYGENATED MYOCYTES

During global ischaemia for various lengths of time followed by reperf usion, the adenine and guanine nucleotide concentrations altered in pa rallel. Measurements of purine precursors and breakdown products sugge sted that GTP was resynthesised from inosine, adenosine or the adenine nucleotides in reversible ischaemia: however, the use of three differ ent inhibitors of the key enzyme in this pathway, IMP-dehydrogenase, w as entirely without effect. To eliminate the endothelial cell barrier, the experiments were repeated with anoxic/reoxygenated cardiac myocyt es. The lower rate of recovery of purine nucleotide triphosphates in m yocytes compared with perfused hearts would tend to confirm the import ant role suggested for endothelial cells in nucleoside salvage. GTP re synthesis took place after reoxygenation by some unknown pathway unaff ected by the presence of large concentrations of an IMP-dehydrogenase inhibitor. The possible relationship of these findings to purinogen, t he recently discovered major source of adenine nucleotides in heart, i s discussed. (C) 1995 Academic Press Limited