摘 要: | Adenosine is an important physiological regulator of the cardiovascular
system. The goal of our study was to assess the expression level
of nucleoside transporters (NT) in diabetic rat cardiomyocytes and to examine
the activities of adenosine metabolizing enzymes. Isolated rat cardiomyocytes
displayed the presence of detectable amounts of mRNA for ENT1,
ENT2, CNT1, and CNT2. Overall adenosine (10 μM) transport in cardiomyocytes
isolated from normal rat was 36 pmol/mg/min. The expression level of
equilibrative transporters (ENT1, ENT2) decreased and of concentrative
transporters (CNT1, CNT2) increased in myocytes isolated from diabetic rat.
Consequently, overall adenosine transport decreased by 30%, whereas Na+–dependent adenosine uptake increased 2–fold, and equilibrative transport
decreased by 60%. The activity ratio of AMP deaminase/5'–nucleotidase in
cytosol of normal cardiomyocytes was 11 and increased to 15 in diabetic cells.
The activity of ecto–5'–nucleotidase increased 2–fold in diabetic cells resulting
in a rise of the activity ratio of ecto–5'–nucleotidase/adenosine deaminase
from 28 to 56.
These results indicate that in rat cardiomyocytes diabetes alters activities
of adenosine metabolizing enzymes in such a way that conversion of AMP to
IMP is favored in the cytosolic compartment, whereas the capability to produce
adenosine extracellularly is increased. This is accompanied by an
increased unidirectional Na+–dependent uptake of adenosine and significantly reduced bidirectional adenosine transport.
|