The proposed research is to determine the rate-limiting steps in myocardial adenine nucleotide synthesis by ascertaining the transport and metabolism of nucleosides in isolated myocardial cells. Specifically, these studies will utilize intact hearts, and isolated heart myocytes and endothelial cells to measure nucleoside transport, incorporation, and 5'nucleotidase activity. These studies are novel because a full picture of energy production and nucleoside transport cannot be obtained with intact tissues. The studies also will address the questions of how nucleosides leave cells, how their loss can be prevented during ischemia, and how nucleotide resynthesis can be enhanced following ischemia. It is thought that by understanding these processes and through use of specific interventions, the hypothesis that myocardial mechanical function is dependent on intracellular nucleotides can be tested. Completion of the proposed studies will help achieve the long term goals of development of interventions to protect ischemic tissue and enhance recovery of normal function in perfused ischemic tissue.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL027336-06
Application #
3339100
Study Section
Cardiovascular Study Section (CVA)
Project Start
1981-06-01
Project End
1989-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Schools of Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Hale, C C; Rovetto, M J (1995) A photoaffinity probe for the cardiac adenosine transporter. Life Sci 57:245-54
Burczynski, F J; Cai, Z S; Moran, J B et al. (1995) Palmitate uptake by cardiac myocytes and endothelial cells. Am J Physiol 268:H1659-66
Dale, W E; Hale, C C; Kim, H D et al. (1991) Myocardial glucose utilization. Failure of adenosine to alter it and inhibition by the adenosine analogue N6-(L-2-phenylisopropyl)adenosine. Circ Res 69:791-9
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
Dale, W E; Tsai, Y S; Jung, C Y et al. (1988) Kinetic characterization and radiation-target sizing of the glucose transporter in cardiac sarcolemmal vesicles. Biochim Biophys Acta 943:360-6
Sunnergren, K P; Rovetto, M J (1987) Myocyte and endothelial injury with ischemia reperfusion in isolated rat hearts. Am J Physiol 252:H1211-7
Geisbuhler, T P; Sergeant, S; Miramonti, F L et al. (1987) Forskolin inhibition of hexose transport in cardiomyocytes. Pflugers Arch 409:158-62
Geisbuhler, T P; Johnson, D A; Rovetto, M J (1987) Cardiac myocyte guanosine transport and metabolism. Am J Physiol 253:C645-51
Sunnergren, K P; Rovetto, M J (1985) The effects of hyaluronidase on interstitial hydration, plasma protein exclusion, and microvascular permeability in the isolated perfused rat heart. Microvasc Res 30:286-97
Rovetto, M J (1985) Myocardial nucleotide transport. Annu Rev Physiol 47:605-16

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