Little is known about the mechanisms by which guanosine and guanine nucleotide metabolism is controlled in the heart, or of the contribution of these compounds to myocardial cell function. The proposed work will utilize both isolated adult heart myocytes and intact heart to determine metabolic pathways for guanine nucleotide synthesis. Transport rates for guanosine and rates of subsequent incorporation of this guanosine into 5' -nucleotides, will be determined using myocytes. The mechanism by which these cells maintain their guanine nucleotide pool also will be examined. Using rates obtained in myocyte experiments, guanosine will be provided to post-ischemic hearts to selectively replenish guanine nucleotides. The contribution of the guanine nucleotide pool to both maintenance of adenine nucleotides and heart performance under normal and post-ischemic conditions will be determined. This approach will allow assessment of the relative contributions of myocyte and non-myocyte cells to guanosine metabolism as well as the role of guanosine and its metabolites in myocyte function. Special attention will be directed to the regulation of guanosine salvage pathways in these studies. The extent to which guanine nucleotide metabolism is involved in phosphatidylinositol turnover, intracellular calcium mobility, and maintenance or cardiac contractility also will be studied. Results of these studies will provide information about guanosine metabolism in normal and ischemic heart, and increase our understanding of the mechanisms by which this metabolism is regulated.
| Geisbuhler, T P; Schwager, T L; Rovetto, M J (1992) Guanosine metabolism in adult rat cardiac myocytes: inhibition by acyclovir and analysis of a metabolic pathway. J Mol Cell Cardiol 24:683-90 |
| Geisbuhler, T P; Rovetto, M J (1991) Guanosine metabolism in adult rat cardiac myocytes: ribose-enhanced GTP synthesis from extracellular guanosine. Pflugers Arch 419:160-5 |
| Geisbuhler, T P; Rovetto, M J (1990) Lactate does not enhance anoxia/reoxygenation damage in adult rat cardiac myocytes. J Mol Cell Cardiol 22:1325-35 |
