Perturbations of sarcolemmal and microsomal enzymes by amphiphilic lipids and drugs.
Sarcolemmal (SL) and microsomal (MC) membranes were prepared from adult canine cardiocytes. SL Na+, K+-ATPase (2.35 mumole/min per mg) was enriched 117-fold over the homogenate and MC rotenone-insensitive NADH cytochrome c reductase (RINCR) was enriched 41-fold. Preincubation of SL with 50 microM arachidonyl-CoA (20:4 CoA) stimulated Na+, K+-ATPase almost 2-fold; 250 microM 20:4 CoA inhibited the enzyme by 85%. However, RINCR was inhibited 80% by only 0.2 microM 20:4 CoA. Thus, each of these myocardial lipid-dependent enzymes showed a different sensitivity to perturbation by lipid amphiphiles. In further experiments, SL preincubated with 50 microM 20:4 CoA + 2.5 mM propranolol (which had no effect alone) exhibited a synergistic inhibition of the Na+, K+-ATPase: The enzymatic activity declined 8.5-fold when compared to sarcolemma treated with 50 microM 20:4 CoA alone. Thus, the presence of lipid amphiphiles may result in greater inhibition of the Na+, K+-ATPase when propranolol is present in the membrane.
Weglicki
W B
WB
Kramer
J H
JH
Kennett
F F
FF
Knauer
T E
TE
Owens
K
K
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D003579:Cytochrome Reductases / Q000037:antagonists & inhibitors*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D008861:Microsomes / Q000187:drug effects* / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology*; D012508:Sarcolemma / Q000187:drug effects* / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000214:Acyl Coenzyme A; D010743:Phospholipids; C026563:arachidonyl-coenzyme A; D002784:Cholesterol; D011433:Propranolol; D003579:Cytochrome Reductases; D009245:NADH Dehydrogenase; D000254:Sodium-Potassium-Exchanging ATPase