Effect of palmitoyl carnitine on Na+, K+-ATPase and adenylate cyclase activity of canine myocardial sarcolemma.
The accumulation of long chain of acyl carnitine, which is thought to exaggerate myocardial ischemic damage, has been demonstrated in ischemic myocardium. The purpose of this study was to determine the effect of palmitoyl carnitine on the Na+, K+-ATPase and adenylate cyclase activity of myocardial sarcolemma in vitro. Controversial views exist at present regarding the effect of palmitoyl carnitine on Na+, K+-ATPase. Wood et al. [23] observed that palmitoyl carnitine inhibited the activity of Na+, K+-ATPase but this inhibition was not observed by Owens et al. [17]. We did observe an inhibition of Na+, K+-ATPase by palmitoyl carnitine. The 50% inhibition of the maximum activity was observed at a palmitoyl carnitine concentration of 110 microM and complete inhibition at 160 microM. Adenylate cyclase activity was inhibited by palmitoyl carnitine irrespective of the assay conditions. The (isoproterenol + GTP)-stimulated activity, fluoride-stimulated activity and basal activity with Mg-ATP or Mn-ATP as a substrate were all inhibited though to varying degrees. The 50% inhibition of adenylate cyclase activity was observed at 84 microM, 94 microM, 200 microM and 105 microM of palmitoyl carnitine in the above mentioned order. The inhibition curve showed a shoulder or even a peak at about 75 microM of palmitoyl carnitine. It is suggested that elevated levels of palmitoyl carnitine in ischemic myocardium may play a role in inhibiting sarcolemmal function.
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives*; D004285:Dogs; D009206:Myocardium / Q000201:enzymology*; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D012508:Sarcolemma / Q000187:drug effects* / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D010172:Palmitoylcarnitine; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase; D002331:Carnitine