SOLUBLE FORMS OF 5'-NUCLEOTIDASE IN RAT AND HUMAN HEART

Intracellular AMP hydrolysis probably produces sufficient adenosine in ischemic heart to exert physiological activity. Because data on adeno sine-producing systems in human heart are scarce, we measured 1) forma tion of adenosine (catabolites) in ischemic human heart slices and 2) cytoplasmic 5'-nucleotidase activity in human left ventricle. We also measured the latter in rat ventricle and cardiomyocytes. During the fi rst 5 min of incubation, adenosine production in slices (n = 5) equale d 26 +/- 10 (SD) nmol . min(-1) . g wet wt(-1), and total AMP content was 0.81 +/- 0.46 mM. Cytoplasmic IMP-preferring 5'-nucleotidase activ ity in homogenates of human heart (N-II, 167 +/- 78 mU/g, n = 23) was significantly higher than that of the AMP-preferring one (N-I, 107 +/- 61 mU/g, n = 24). Both isozymes were two to three times more active i n rat heart than in human heart. Rat cardiomyocytes contained comparab le amounts of the two 5'-nucleotidases. Kinetics of N-I isolated from explanted human heart displayed features similar to the enzyme from an imal heart, with a Michaelis constant of 1.5 mM under maximally stimul ated conditions. This form can provide the amount of adenosine found i n ischemic slices. In conclusion, human heart shows lower cytosolic 5' -nucleotidase activities than rat heart. Nevertheless, cytosolic 5'-nu cleotidase activity in human heart can easily account for adenosine fo rmation during ischemia.