Formation of Adenosine in the Heart from Extracellular Adenine Nucleotides

Abstract

Adenine nucleotides intracoronarily applied are rapidly degraded during single passage through the heart (Baer et al., 1968; Paddle et al., 1987; Schrader et al., 1982; Ronca-Testoni et al, 1982; Fleetwood et al., 1989). The pattern of catabolites formed is consistent with the major pathway of metabolism being sequential dephosphorylation of ATP –> ADP –> AMP –> adenosine (Fleetwood et al., 1989). Ecto-adenosinetriphosphatase (ATPase), -adenosinediphosphatase (ADPase) and ecto 5’-nucleotidase have been demonstrated in cultured endothelial cells (Gordon et al., 1986). These enzymes are mainly responsible for the rapid catabolism of adenine nucleotides in the coronary circulation. To what extend cardiomyocytes can metabolize extracellular adenine nucleotides appears to be species dependent (Newby et al., 1987). Guinea pig cardiomyocytes appear not to exhibit ecto 5’-nucleotidase activity (Dendorfer et al., 1987). The further catabolism of adenosine to inosine, hypoxanthine and uric acid is exclusively by endothelial cells. Nucleoside Phosphorylase (Rubio et al., 1972) and xanthine oxidase (Schoutsen et al., 1987) are cytosolic marker enzymes of coronary endothelial cells although there are pronounced species differences in the case of xanthine oxidase. In the presence of a nucleoside transport inhibitor such as dipyridamole the catabolism of extracellular ATP only proceeds to the stage of adenosine (Gordon et al., 1986), again demonstrating that the metabolism of adenosine occurs intracellularly.