title: Inorganic phosphate as regulator of adenosine formation in isolated guinea pig hearts.
abstract: 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.
authors.affiliation: Department of Physiology, Michigan State University, East Lansing 48824, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Gorman
authors.forename: M X
authors.initials: MX
authors.lastname: He
authors.forename: C S
authors.initials: CS
authors.lastname: Hall
authors.forename: H V
authors.initials: HV
authors.lastname: Sparks
mesh_terms: 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
chemical_list: D000085:Acetates; D006146:Guanidines; D010710:Phosphates; D011422:Propionates; D000249:Adenosine Monophosphate; D003847:Deoxyglucose; D000248:Adenosine Kinase; D000241:Adenosine; C005775:guanidinopropionic acid