GUANOSINE METABOLISM IN ADULT-RAT CARDIAC MYOCYTES - INHIBITION BY ACYCLOVIR AND ANALYSIS OF A METABOLIC PATHWAY

The metabolic fate of transported guanosine was examined in adult rat cardiac myocytes. Freshly isolated cells were incubated with 50 μm 8-[3H]-guanosine and the purine nucleoside phosphorylase (PNP) inhibitor acyclovir, and the nucleotide products extracted and examined for radiolabel distribution. Acyclovir inhibited guanosine incorporation into the 5′-nucleotide pool up to 66%. The drug did not inhibit guanosine transport. Other experiments using 5′-[3H]-guanosine and 8-[14C]-guanosine in concert as metabolic tracers showed both tritium and radiocarbon in the guanine nucleotide products. We concluded from this study that both a kinase (probably adenosine kinase) and the enzyme pair purine nucleoside phosphorylase/hypoxanthine-guanine phosphoryibosyltransferase are responsible for guanosine salvage in heart cells. © 1992.