INORGANIC-PHOSPHATE AS REGULATOR OF ADENOSINE FORMATION IN ISOLATED GUINEA-PIG HEARTS

This study evaluated cytosolic P-i as an independent regulator of card iac adenosine formation by dissociating changes in P-i from changes in AMP and ADP. Myocardial high-energy phosphates (HEP), measured by P-3 1 nuclear magnetic resonance spectroscopy, were depleted acutely by pe rfusing isolated guinea pig hearts with 2-deoxyglucose (2-DG), and the effects of 2-DG were compared with a norepinephrine infusion producin g similar changes in HEP. 2-DG treatment resulted in lower adenosine r elease (R(ado)) (54 +/- 18 vs. 622 +/- 199 pmol . min(-1). g(-1)) and P-i concentration ([P-i]) (0.5 +/- 0.1 vs. 6.0 +/- 0.9 mM) than norepi nephrine despite similar AMP concentration ([AMP]). Chronic phosphocre atine depletion produced by beta-guanidinopropionic acid feeding also reduced R(ado) and P-i during hypoxia. Replacement of perfusate glucos e and pyruvate with acetate increased R(ado) (from 39 +/- 12 to 356 +/ - 100 pmol . min(-1). g(-1)) and [P-i] (from 2.0 +/- 0.5 to 5.1 +/- 0. 6 mM) with no change in cytosolic [AMP]. Adenosine kinase isolated fro m guinea pig hearts was inhibited by [P-i] values seen during hypoxia or hypoperfusion. We conclude that cytosolic [P-i] can be an important regulator of cardiac adenosine formation through inhibition of adenos ine kinase.