Caffeine decreases malonyl-CoA in isolated perfused skeletal muscle of rats.
The regulation of acetyl-CoA carboxylase and malonyl-CoA levels in skeletal muscle may involve a calcium-dependent mechanism. To examine the effects of increased free sarcoplasmic calcium concentrations on malonyl-CoA in skeletal muscle, isolated hindlimbs of rats were perfused for 30 min with a medium containing bovine red blood cells, bovine serum albumin, 200 microU/ml insulin, and 10 mM glucose in Krebs-Henseleit buffer and caffeine at 0, 0.12, 0.5, or 3 mM. Malonyl-CoA decreased from control (no caffeine) values of 1.34 +/- 0.9 to 0.95 +/- 0.12 pmol/mg in gastrocnemius-plantaris muscles perfused with 0.12 and 0.5 mM caffeine and to 0.63 +/- 0.07 pmol/mg in the muscles perfused with 3 mM caffeine. Adenosine 3',5'-cyclic monophosphate (cAMP) increased from 0.24 +/- 0.02 to 0.32 +/- 0.04 nmol/g, and AMP decreased from 83 +/- 8 to 53 +/- 3 nmol/g in response to 3 mM caffeine. Citrate and ATP were unaffected by caffeine. A decline in malonyl-CoA with 0.12 and 0.5 mM caffeine without an increase in cAMP supports the hypothesis that a calcium-dependent mechanisms of acetyl-CoA carboxylase and malonyl-CoA regulation exists, but a cAMP-dependent mechanism may also be involved with 3 mM caffeine.
Maclean
P S
PS
Zoology Department, Brigham Young University, Provo, Utah 84602, USA.
Winder
W W
WW
D000103:Acetyl-CoA Carboxylase / Q000187:drug effects / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006614:Hindlimb; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008316:Malonyl Coenzyme A / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology*; D010101:Oxygen Consumption; D010477:Perfusion; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007773:Lactates; D010725:Phosphocreatine; D019344:Lactic Acid; D002110:Caffeine; D000249:Adenosine Monophosphate; D008316:Malonyl Coenzyme A; D006003:Glycogen; D000242:Cyclic AMP; D000103:Acetyl-CoA Carboxylase; D005947:Glucose