Adenine nucleotide synthesis from inosine during normoxia and after ischaemia in the isolated perfused rat heart

1985 ◽  
Vol 63 (9) ◽  
pp. 1159-1164 ◽  
Author(s):  
J. Aussedat ◽  
M. Verdys ◽  
A. Rossi

[14C]inosine in a range of concentrations of 20 μM to 1 mM was administered-to the isolated perfused rat heart for 30 min. The incorporation of the nucleoside into myocardial adenine nucleotides increased for extracellular concentrations of the precursor up to 50 μM, reaching a plateau at 60 nmol∙g−1∙30 min−1 with concentrations ranging between 50 and 200 μM. The supply of 500 μM and 1 mM of inosine induced a further increase in cardiac adenine nucleotide synthesis to about 200 nmol∙g−1∙30 min−1. When supplied during low flow ischaemia (0.5 mL∙min−1, 30 min.), 1 mM of inosine protected the heart against ATP degradation, while 100 μM of inosine was inefficacious. In the presence of 1 mM of inosine on reperfusion the adenine nucleotide content of the heart was similar to that observed in the absence of the nucleoside. The incorporation of [14C]inosine into adenine nucleotides was, in this last condition, below the value measured before ischaemia. Inosine administration was effective in protecting the heart against ischaemic breakdown of glycogen and favoured postischaemic restoration of glycogen stores.

1990 ◽  
Vol 66 (2) ◽  
pp. 302-310 ◽  
Author(s):  
G K Asimakis ◽  
G S Sandhu ◽  
V R Conti ◽  
L A Sordahl ◽  
J B Zwischenberger

1978 ◽  
Vol 176 (2) ◽  
pp. 485-493 ◽  
Author(s):  
David J. Bates ◽  
David Perrett ◽  
John Mowbray

1. The contents of the major purine nucleotides in the isolated non-working perfused rat heart varied systematically during 80min of perfusion. In particular the amounts of ATP, ADP, GTP, cyclic AMP and cyclic GMP in the well-oxygenated myocardium showed changes ranging from 25 to 60% of the mean concentrations. The apparent periodicity was about 30min for some and about 60min for other nucleotides. 2. These data are in contrast with measurements of parameters reflecting heart performance, which remained constant over this period of perfusion. 3. The ATP/ADP ratio, the cyclic AMP content, the GTP content and the GTP/GDP ratio in the tissue bore a constant relationship to one another, and all showed the same temporal variation. 4. Increasing the energy demand on the heart by administration of bovine somatotropin (1μg/ml) tended to damp the variations, and generally lower the content of all the nucleotides. 5. The total extractable adenine nucleotide pool also showed systematic temporal variations of as much as 1.3μmol/g wet wt. of tissue within 10min. 6. These variations could not be accounted for as inter-conversion with adenosine, other purine nucleotides, nucleosides or purine-degradation products either in the tissue or in the perfusion medium. No evidence was found in this preparation of the purine nucleotide oscillations described by Lowenstein and his co-workers [see Tornheim & Lowenstein (1975) J. Biol. Chem.250, 6304–6314]. 7. Further, the pool size increases cannot be satisfactorily explained by either synthesis de novo or the breakdown of any purine macromolecular species in the cell. Thus it is suggested that an unsuspected substantial storage form of purine nucleotide may exist in heart.


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