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 microM 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 phosphoribosyltransferase are responsible for guanosine salvage in heart cells.
Geisbuhler
T P
TP
Department of Physiology, University of Missouri, Columbia 65212.
Schwager
T L
TL
Rovetto
M J
MJ
D000212:Acyclovir / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D006151:Guanosine / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism*; D051381:Rats
D006151:Guanosine; D011683:Purine-Nucleoside Phosphorylase; D007041:Hypoxanthine Phosphoribosyltransferase; D000212:Acyclovir