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Inorganic phosphate as regulator of adenosine formation in isolated guinea pig hearts

M W Gorman1, M X He, C S Hall

  • 1Department of Physiology, Michigan State University, East Lansing 48824, USA.

The American Journal of Physiology
|February 1, 1997
PubMed

Insights

This study shows inorganic phosphate (P(i)) regulates cardiac adenosine formation by inhibiting adenosine kinase. Lower P(i) levels reduce adenosine release, impacting heart function during stress.

Area of Science:

  • Cardiovascular Physiology
  • Biochemistry
  • Cellular Metabolism

Background:

  • Cardiac adenosine formation is crucial for regulating myocardial blood flow and energy metabolism.
  • Cytosolic inorganic phosphate (P(i)) and adenine nucleotides (AMP, ADP) are known regulators of adenosine production.
  • Previous studies have not fully dissociated the independent role of P(i) from AMP and ADP in regulating cardiac adenosine.

Purpose of the Study:

  • To evaluate cytosolic inorganic phosphate (P(i)) as an independent regulator of cardiac adenosine formation.
  • To dissociate the effects of P(i) changes from simultaneous changes in AMP and ADP.
  • To investigate the mechanism by which P(i) influences adenosine production.

Main Methods:

  • Utilized isolated guinea pig hearts perfused with 2-deoxyglucose (2-DG) to acutely deplete myocardial high-energy phosphates (HEP).
  • Compared 2-DG effects with norepinephrine infusion to achieve similar HEP depletion.
  • Employed chronic phosphocreatine depletion via beta-guanidinopropionic acid feeding.
  • Assessed adenosine release (R(ado)), cytosolic P(i) ([P(i)]), and AMP ([AMP]) concentrations.
  • Investigated the effect of P(i) on isolated cardiac adenosine kinase activity.

Main Results:

  • 2-DG treatment significantly lowered R(ado) and [P(i)] compared to norepinephrine, despite similar [AMP].
  • Chronic phosphocreatine depletion also reduced R(ado) and [P(i)] during hypoxia.
  • Replacing perfusate glucose/pyruvate with acetate increased R(ado) and [P(i)] without altering [AMP].
  • In vitro studies demonstrated that cytosolic [P(i)] inhibits cardiac adenosine kinase.

Conclusions:

  • Cytosolic inorganic phosphate (P(i)) acts as an independent regulator of cardiac adenosine formation.
  • P(i) exerts its regulatory effect through the inhibition of adenosine kinase.
  • These findings highlight the critical role of P(i) in modulating cardiac adenosine levels, particularly under conditions of metabolic stress such as hypoxia or hypoperfusion.

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