Effects of fasting, hypoxia, methylpalmoxirate and oxfenicine on the tissue-levels of long-chain acyl CoA and acylcarnitine in the rat atria.
During hypoxia the atria from fasted rats exhibit a faster decline in the pacemaker and contractile activities than those from fed rats. Oxfenicine and methylpalmoxirate, inhibitors of carnitine palmitoyltransferase 1 (CPT 1), ameliorate these disturbances. Since the fasted rat atria have greater triacylglycerol stores and a faster lipolysis, and CPT 1 funnels fatty acid into beta-oxidation, the effects of fasting could be ascribed to the accumulation of amphipathic metabolites such as long-chain acyl CoA (LCCoA) and long-chain acylcarnitine (LCCa). Hence, this investigation aimed to assess whether the levels of these metabolites correlate with the effects of fasting and CPT 1 inhibitors. At the end of the prehypoxic equilibration period the fasted rat atria had a 6.5-fold greater content of LCCa than those of the fed rats and methylpalmoxirate impeded the increase. During hypoxia the LCCoA content increased 9-fold in the fasted rat atria, LCCa levels were 3.6-fold greater in the fasted than in the fed group, and free-CoA and free-carnitine showed a significant fall. The increases of LCCoA and LCCa as well as the fall in free-CoA were abolished by both inhibitors. The decrease of free-carnitine was impeded by methylpalmoxirate, but oxfenicine unexpectedly decreased its concentration in both nutritional groups. These data suggest that: (1) the atrial CPT 1 activity is enhanced during fasting, (2) in the hypoxic atria levels of LCCoA and LCCa were closely correlated with the noxious effects of fasting and the amelioration effected by CPT 1 inhibitors, and (3) the effects of amphipathic metabolites during oxygen deprivation can be attenuated by pharmacological interventions.
Varela
A
A
Cátedra de Fisiología, Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
Carregal
M
M
Testoni
G
G
Dalamon
V
V
Savino
E A
EA
D000214:Acyl Coenzyme A / Q000032:analysis* / Q000096:biosynthesis; D000332:Aerobiosis; D000818:Animals; D002331:Carnitine / Q000032:analysis* / Q000096:biosynthesis; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015687:Cell Hypoxia; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D005215:Fasting / Q000378:metabolism*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000032:analysis* / Q000096:biosynthesis; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000214:Acyl Coenzyme A; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D009124:Muscle Proteins; D011422:Propionates; C023010:4-hydroxyphenylglycine; D002334:Carnitine O-Palmitoyltransferase; C017522:methyl 2-tetradecylglycidate; D002331:Carnitine; D005998:Glycine