The control of adenosine concentration in polymorphonuclear leucocytes, cultured heart cells and isolated perfused heart from the rat.
Rat polymorphonuclear leucocytes or neonatal-rat heart cells in culture were treated with 2'-deoxycoformycin and 5-iodotubercidin at concentrations that inhibited adenosine deaminase (EC 3.5.4.4) and adenosine kinase (EC 2.7.1.20) inside the intact cells, and the rate of adenosine accumulation was determined. The basal rate of adenosine formation was 2% (polymorphonuclear leucocytes) or 9% (heart cells) of the maximal activity of adenosine kinase also measured in intact cells. Greatly increased rates of adenosine formation were observed during adenine nucleotide catabolism. This condition also led to a decrease in adenosine kinase activity. When isolated rat hearts were perfused with 5-iodotubercidin alone at a concentration which inhibited adenosine kinase, no increase in tissue or perfusate adenosine or inosine concentration was observed. However, perfusion with hypoxic buffer or infusion of adenosine into the coronary circulation at a rate (20 nmol/min) equivalent to 40% of the activity of adenosine kinase caused large increases in effluent perfusate adenosine and inosine concentrations. These data argue unanimously against the existence of a substrate cycle controlling adenosine concentration. They suggest instead that an increase in the rate of adenosine formation is the principal cause of elevations in adenosine concentration during ATP catabolism.
D000241:Adenosine / Q000096:biosynthesis / Q000378:metabolism*; D000248:Adenosine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D015649:Pentostatin; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology
D003070:Coformycin; C034214:5-iodotubercidin; D015649:Pentostatin; D000248:Adenosine Kinase; D000241:Adenosine; D014372:Tubercidin