Adenosine deaminase inhibition and myocardial adenosine metabolism during ischemia.
It is generally assumed that myocardial adenine nucleotides are broken down (e.g., during ischemia) via AMP----adenosine----inosine, but contribution of the pathway AMP----IMP----inosine cannot be excluded. The catabolism of exogenously added adenosine (1-20 microM) was studied in isolated rat hearts. All catabolites (i.e., inosine, hypoxanthine, xanthine, and uric acid) were measured together with nonmetabolized adenosine. Even at low (1 microM) adenosine concentrations, deamination accounted for 60% of adenosine disappearing from the perfusate. The adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) (5 and 50 microM) was infused together with adenosine (5 microM). These two concentrations of EHNA inhibited deamination of exogenous adenosine by 65 and 91%, respectively. When hearts were made ischemic by reduction of perfusion pressure, addition of EHNA raised the adenosine release from 1.4 to 9.8 nmole/min per gram wet wt., but surprisingly, the release of inosine and oxypurines (8 nmole/min per g wet wt.) did not change. These results suggest that considerable breakdown of myocardial adenine nucleotides can occur via the AMP----IMP----inosine pathway instead of AMP----adenosine----inosine. The rate of total purine release is probably not a good measure of intracellular adenosine formation.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism*; D058892:Adenosine Deaminase Inhibitors; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000201:enzymology*; D007291:Inosine Monophosphate / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D011687:Purines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D058892:Adenosine Deaminase Inhibitors; D011687:Purines; D007291:Inosine Monophosphate; D000249:Adenosine Monophosphate; C010192:9-(2-hydroxy-3-nonyl)adenine; D009700:Nucleoside Deaminases; D000225:Adenine; D000241:Adenosine