The contribution of neuronal
ATP to interstitial
adenosine levels was investigated in isolated perfused rat hearts. Ventricular surface transudates, representing interstitial fluid, were analyzed for
norepinephrine,
ATP, and
adenosine. Exocytotic release of
norepinephrine was induced by electrical stimulation of cardiac efferents emanating from the stellate ganglion.
Ganglion stimulation increased contractility, interstitial
norepinephrine,
ATP, and
adenosine. Interstitial
adenosine was 11- to 27-fold higher than interstitial
ATP, suggesting that the released
ATP is unlikely the only source of
adenosine. In the presence of
AOPCP (alpha,beta-methyleneadenosine 5'-diphosphate), an
ecto-5'-nucleotidase inhibitor, the
ganglion-stimulated increase in interstitial
ATP and
adenosine reached levels similar to those in the absence of
AOPCP, also suggesting that
adenosine does not derive from extracellular
ATP. The perfusate Ca2+ was raised from 1 to 4 mM to determine the importance of the enhanced contractile function on the levels of
norepinephrine,
ATP, and
adenosine. The results were increases in contractility and interstitial
norepinephrine,
ATP, and
adenosine, which were not suppressed with
atenolol, indicating a
norepinephrine-independent release of
ATP and
adenosine.
Reserpine treatment and administration of
guanethidine depleted the
catecholamine stores and diminished the
catecholamine release, respectively. However, neither agent altered Ca2+-induced increases in
ATP and
adenosine. It is concluded that the amount of neuronal-derived
ATP is low and most likely does not contribute significantly to interstitial levels of
adenosine. Furthermore, elevations in interstitial
norepinephrine,
ATP, and
adenosine are associated with neuronal-independent increases in contractile function.