The contents of high-energy phosphates in different fibre types in skeletal muscles from rat, guinea-pig and man.

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.

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Adenosine deaminase inhibitors attenuate ischemic injury and preserve energy balance in isolated guinea pig heart

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.265.4.h1249 ◽

1993 ◽

Vol 265 (4) ◽

pp. H1249-H1256 ◽

Cited By ~ 3

Author(s):

G. S. Sandhu ◽

A. C. Burrier ◽

D. R. Janero

Keyword(s):

Guinea Pig ◽

Adenosine Deaminase ◽

Flow Rate ◽

Coronary Flow ◽

Contractile Function ◽

Ischemia Reperfusion ◽

Ischemic Injury ◽

High Energy ◽

High Energy Phosphates ◽

Postischemic Recovery

We investigated the effect of the adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and coformycin on high-energy phosphate metabolism, tissue nucleotides and nucleosides, and recovery of contractile function in isolated, perfused guinea pig hearts. EHNA and coformycin (10 microM) improved postischemic recovery of contractile function approximately 85% and enhanced coronary flow rate in reperfused tissue approximately 40%. The protective effect of EHNA on recovery of contractile function was concentration dependent. Although adenosine (10 microM) increased coronary flow rate on reperfusion approximately twofold over vehicle, it failed to improve postischemic recovery of contractile function. EHNA and coformycin preserved cardiac ATP levels and increased endogenous tissue adenosine during ischemia. During reperfusion, these agents enhanced recovery of high-energy phosphates approximately twofold and potentiated adenosine release into the perfusate with concentration dependency. Furthermore, EHNA and coformycin reduced the extent of myocardial ischemia-reperfusion injury, as indicated by the approximately 55% reduction in creatine phosphokinase release. We conclude that inhibitors of adenosine deaminase attenuate myocardial ischemic injury and improve postischemic recovery of contractile function and metabolism through endogenous myocardial adenosine enhancement and ATP preservation.

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Effects of nonspecific smooth muscle relaxants on tissue concentrations of high energy phosphates and mechanical activity of normal polarized and depolarized intestinal smooth muscles from guinea pig.

The Japanese Journal of Pharmacology ◽

10.1254/jjp.30.405 ◽

1980 ◽

Vol 30 (4) ◽

pp. 405-412 ◽

Cited By ~ 2

Author(s):

Issei TAKAYANAGI ◽

Akira KARASAWA ◽

Yutaka KASUYA

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Smooth Muscles ◽

High Energy ◽

Muscle Relaxants ◽

Mechanical Activity ◽

High Energy Phosphates ◽

Tissue Concentrations ◽

Intestinal Smooth Muscles

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Effects of high-energy phosphates on carbachol-evoked cationic current in single smooth muscle cells from guinea-pig ileum.

The Journal of Physiology ◽

10.1113/jphysiol.1995.sp020760 ◽

1995 ◽

Vol 485 (3) ◽

pp. 659-669 ◽

Cited By ~ 6

Author(s):

A Bakhramov

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Smooth Muscle Cells ◽

Muscle Cells ◽

High Energy ◽

High Energy Phosphates ◽

Guinea Pig Ileum ◽

Cationic Current

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ATP from glycolysis is required for normal sodium homeostasis in resting fast-twitch rodent skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.281.3.e479 ◽

2001 ◽

Vol 281 (3) ◽

pp. E479-E488 ◽

Cited By ~ 43

Author(s):

Ken Okamoto ◽

Weiyang Wang ◽

Jan Rounds ◽

Elizabeth A. Chambers ◽

Danny O. Jacobs

Keyword(s):

Skeletal Muscles ◽

Iodoacetic Acid ◽

High Energy ◽

Sodium Content ◽

Intracellular Sodium ◽

High Energy Phosphates ◽

Sodium Homeostasis ◽

Carbonyl Cyanide ◽

Fast Twitch

Myocellular sodium homeostasis is commonly disrupted during critical illness for unknown reasons. Recent data suggest that changes in intracellular sodium content and the amount of ATP provided by glycolysis are closely related. The role of glycolysis and oxidative phosphorylation in providing fuel to the Na+-K+ pump was investigated in resting rat extensor digitorum longus muscles incubated at 30°C for 1 h. Oxidative inhibition with carbonyl cyanide m-chlorophenylhydrazone, known as CCCP (0.2 μM), or by hypooxygenation did not alter myocellular sodium or potassium content ([Na+]i, [K+]i, respectively), whereas treatment with iodoacetic acid (0.3 mM), which effectively blocked glycolysis, dramatically increased [Na+]i and the [Na+]i/[K+]i ratio. Experiments using ouabain and measurements of myocellular high-energy phosphates indicate that Na+-K+-ATPase activity is only impaired when glycolysis is inhibited. The data suggest that normal glycolysis is required to regulate intracellular sodium in fast-twitch skeletal muscles, because it is the predominant source of the fuel for the Na+-K+-ATPase.

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Ischemic cardioprotection by ATP-sensitive K+ channels involves high-energy phosphate preservation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.265.5.h1809 ◽

1993 ◽

Vol 265 (5) ◽

pp. H1809-H1818 ◽

Cited By ~ 18

Author(s):

C. D. McPherson ◽

G. N. Pierce ◽

W. C. Cole

Keyword(s):

Guinea Pig ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Creatine Phosphate ◽

High Energy ◽

Mechanical Activity ◽

High Energy Phosphates ◽

High Energy Phosphate ◽

K Channels ◽

Ischemic Contracture

We previously demonstrated that ATP-sensitive K+ channels (KATP) protect the guinea pig myocardium against ischemia-reperfusion injury (Cole et al., Circ. Res. 69: 571-581, 1991), but the cellular alterations leading to ischemic injury affected by KATP remain to be defined. This study investigates the relationship between activation of KATP and preservation of high-energy phosphates during global no-flow ischemia in arterially perfused guinea pig right ventricular walls. Electrical and mechanical activity were recorded via intracellular microelectrodes and a force transducer. Glibenclamide (10 and 50 microM) and pinacidil (10 microM) were used to modulate KATP. ATP and creatine phosphate (CP) levels were determined at the end of no-flow ischemia by enzymatic analysis. Preparations were subjected to 1) 20 min no-flow +/- glibenclamide (10 or 50 microM), 2) 30 min no-flow +/- pinacidil (10 microM) or pinacidil (10 microM) and glibenclamide (50 microM), or 3) 40 or 50 min of control perfusion before rapid freezing in liquid nitrogen. Pinacidil (10 microM) enhanced ischemic shortening of action potential duration (APD) and early contractile failure, prevented ischemic contracture, and inhibited high-energy phosphate depletion during ischemia. Glibenclamide (50 microM) inhibited the effects of pinacidil (10 microM) on electromechanical function and preservation of ATP and CP. Glibenclamide (10 microM) alone inhibited the early decline in APD and produced earlier ischemic contracture but did not enhance ATP or CP depletion compared with untreated tissues during 20 min of no-flow. Glibenclamide (50 microM) produced a greater inhibition of APD shortening in early ischemia, further decreased the latency to ischemic contracture, and caused enhanced ischemic depletion of ATP. The data indicate the changes in electrical activity induced by KATP indirectly preserve high-energy phosphates and reduce injury associated with ischemia. However, the data also suggest the possible presence of additional mechanisms for cardioprotection by KATP.

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