Inorganic phosphate as regulator of adenosine formation in isolated guinea pig hearts.
This study evaluated cytosolic P(i) as an independent regulator of cardiac adenosine formation by dissociating changes in P(i) from changes in AMP and ADP. Myocardial high-energy phosphates (HEP), measured by (31)P nuclear magnetic resonance spectroscopy, were depleted acutely by perfusing isolated guinea pig hearts with 2-deoxyglucose (2-DG), and the effects of 2-DG were compared with a norepinephrine infusion producing similar changes in HEP. 2-DG treatment resulted in lower adenosine release (R(ado)) (54 +/- 18 vs. 622 +/- 199 pmol x min(-1) x g(-1)) and P(i) concentration ([P(i)]) (0.5 +/- 0.1 vs. 6.0 +/- 0.9 mM) than norepinephrine despite similar AMP concentration ([AMP]). Chronic phosphocreatine depletion produced by beta-guanidinopropionic acid feeding also reduced R(ado) and P(i) during hypoxia. Replacement of perfusate glucose and pyruvate with acetate increased R(ado) (from 39 +/- 12 to 356 +/- 100 pmol x min(-1) x 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 from 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 adenosine kinase.
Gorman
M W
MW
Department of Physiology, Michigan State University, East Lansing 48824, USA.
He
M X
MX
Hall
C S
CS
Sparks
H V
HV
D000085:Acetates / Q000494:pharmacology; D000241:Adenosine / Q000096:biosynthesis* / Q000378:metabolism; D000248:Adenosine Kinase / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism / Q000502:physiology*; D011422:Propionates / Q000494:pharmacology
D000085:Acetates; D006146:Guanidines; D010710:Phosphates; D011422:Propionates; D000249:Adenosine Monophosphate; D003847:Deoxyglucose; D000248:Adenosine Kinase; D000241:Adenosine; C005775:guanidinopropionic acid