Adenosine deaminase inhibition and myocardial purine release during normoxia and ischaemia.
Quantitative determination of myocardial adenosine formation and breakdown is necessary to gain insight into the mechanism and regulation of its physiological actions. Deamination of adenosine was studied in isolated perfused rat hearts by infusion of adenosine (1 to 20 mumol X litre-1). All catabolites in the perfusates (inosine, hypoxanthine, xanthine and uric acid) were measured, as well as unchanged adenosine. Apparent uptake of adenosine was determined; it increased linearly with the concentration of adenosine infused. Adenosine was predominantly deaminated, even at low (1 mumol X litre-1) concentration. The inhibitory capacity of the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) was determined, while 5 mumol X litre-1 adenosine was infused. EHNA inhibited the apparent adenosine deaminase activity for 62 and 92% at 5 and 50 mumol X litre-1, respectively. When 50 mumol X litre-1 EHNA was infused into normoxic hearts, release of adenosine was significantly elevated, as was coronary flow. Induction of ischaemia increased total purine release four-to fivefold. Infusion of EHNA into ischaemic hearts did not alter total purine release, but adenosine release increased from 15 to 60% of total purines. However, when EHNA was present, a large part of total purine release still existed of inosine, hypoxanthine, xanthiner and uric acid. This was 83% during normoxia and 40% during ischaemia. These results suggest significant contribution of IMP and GMP breakdown to purine release from isolated perfused rat hearts.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation; D003641:Deamination; D003864:Depression, Chemical; D006321:Heart / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D009700:Nucleoside Deaminases / Q000378:metabolism*; D010101:Oxygen Consumption; D010477:Perfusion; D011687:Purines / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D011687:Purines; D000249:Adenosine Monophosphate; C010192:9-(2-hydroxy-3-nonyl)adenine; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000225:Adenine; D000241:Adenosine