Myocardial adenosine cycling rates during normoxia and under conditions of stimulated purine release.
Formation and rephosphorylation of adenosine (adenosine cycling) was studied in isolated rat hearts during normoxia and under conditions of stimulated purine formation. Hearts were infused with an inhibitor of adenosine kinase (5-iodotubercidin, 2 microM). In addition, perfusions were carried out with or without acetate, which is converted into acetyl-CoA, with simultaneous breakdown of ATP to AMP and purines. We found a linear, concentration-dependent, increase in normoxic purine release by acetate (5-20 mM). Differences in total purine release with or without iodotubercidin were taken as a measure of adenosine cycling. In normoxic hearts, iodotubercidin caused a minor increase in purine release (2.7 nmol/min per g wet wt.). Acetate (12.5 mM) increased purine release by 4.9 nmol/min per g, and its combination with inhibitor gave a large increase, by 14.2 nmol/min per g. This indicates a strongly increased adenosine cycling rate during acetate infusion. However, no significant differences in purine release were observed when iodotubercidin was infused during hypoxia, anoxia or ischaemia. The hypothesis that adenosine cycling is near-maximal during normoxia was not confirmed. Increased myocardial adenosine formation appears to be regulated by the availability of AMP and not by inhibition of adenosine kinase. This enzyme mainly functions to salvage adenosine in order to prevent excessive loss of adenine nucleotides.
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology; D014527:Uric Acid / Q000378:metabolism
D000085:Acetates; D011687:Purines; C034214:5-iodotubercidin; D014527:Uric Acid; D007288:Inosine; D000241:Adenosine; D014372:Tubercidin; D019342:Acetic Acid; D010100:Oxygen