Nucleoside transport inhibition and the release of purine metabolites from hypoperfused isolated guinea pig hearts

Abstract

Van Belle, H., J. Wynants and F. Goossens: Nucleoside transport inhibition and the release of purine metabolites from hypoperfused isolated guinea pig hearts. Drug Dev. Res. 8:425-431, 1986. Hypoperfusion elicited a marked but transient release from isolated guinea pig hearts of inorganic phosphate, inosine, hypoxanthine, xanthine, and uridine, but had no effect on the release of uric acid, uracil, and adenosine. Lack of increased formation of adenosine, as well as a clearcut effect of hypoperfusion on uridine release, suggest that the purine catabolites did not originate from either cyclic AMP or from ATP released with catecholamines during ischemia. They merely point to a particular sensitivity of some cells to ischemia whereby the nucleotides are rapidly degraded and released into the interstitium.Inclusion at low concentrations (5 x lo-* M) of a nucleoside transport inhibitor, such as the water soluble analogue of mioflazine, drastically reduced the basal release of most of the metabolites and completely suppressed the effect of hypoperfusion. This effect is specifically ascribed to nucleoside-transport inhibition since no marked change was observed on the release of inorganic phosphate.