Inorganic phosphate as a regulator of adenosine formation in the
isolated guinea pig heart.
Gorman, Mark W, Miao-Xiang He, Carolyn S. Hall, and Harvey V Sparks.
Department of Physiology, Michigan State University, East Lansing,
MI 48824
APStracts 3:0367H, 1996.
This study evaluated cytosolic Pi as an independent regulator of
cardiac adenosine formation by dissociating changes in Pi from
changes in AMP and ADP. Myocardial high energy phosphates (HEP),
measured by 31P-NMR spectroscopy, were depleted acutely by perfusing
isolated guinea pig hearts with 2-deoxyglucose (2DG), and the effects
of 2DG were compared to a norepinephrine infusion producing similar
changes in HEP. 2DG treatment resulted in lower adenosine release
(Rado) (54 18 vs. 622 199 pmol/min/g) and [Pi] (0.5 0.1 vs. 6.0 0.9
mM) than norepinephrine despite similar [AMP]. Chronic
phosphocreatine depletion produced by b-guanidinopropionic acid (GPA)
feeding also reduced Rado and Pi during hypoxia. Replacement of
perfusate glucose and pyruvate with acetate increased Rado (39 12 to
356 100 pmol/min/g) and [Pi] (2.0 0.5 to 5.1 0.6 mM) with no change
in cytosolic [AMP]. Adenosine kinase isolated from guinea pig hearts
was inhibited by Pi concentrations seen during hypoxia or
hypoperfusion. We conclude that cytosolic [Pi] can be an important
regulator of cardiac adenosine formation through inhibition of
adenosine kinase.
Received 15 May 1996; accepted in final form 2 August 1996.
APS Manuscript Number H443-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996