Differences between human, rat and guinea pig hepatocyte cultures. A comparative study of their rates of beta-oxidation and esterification of palmitate and their sensitivity to R-etomoxir.
Rat hepatocyte cultures have higher rates of beta-oxidation of palmitate and lower rates of esterification to glycerolipid than human or guinea pig hepatocytes. The R-enantiomer of etomoxir (sodium 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate), a hypoglycaemic compound and inhibitor of carnitine palmitoyltransferase I, inhibited palmitate beta-oxidation in all three species, but the sensitivity to inhibition was highest in human hepatocytes and lowest in rat hepatocytes. The concentration causing half-maximal inhibition was approximately: 0.1 microM in human; 1 microM in guinea pig and 10 microM in rat hepatocytes. In human and in guinea pig hepatocytes the inhibition of beta-oxidation by R-etomoxir was associated with an increase in the esterification of palmitate but in rat hepatocytes R-etomoxir lowered the total rate of palmitate metabolism. The S-enantiomer of etomoxir had no significant effect on beta-oxidation or esterification of palmitate in any of the three species. It is concluded that there are significant differences between human, rat and guinea pig hepatocytes, not only in the relative partitioning of palmitate between beta-oxidation and esterification, but also in the sensitivity to an inhibitor of carnitine palmitoyltransferase I.
Agius
L
L
Department of Medicine, Medical School, University of Newcastle upon Tyne, U.K.
Peak
M
M
Sherratt
S A
SA
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004852:Epoxy Compounds / Q000494:pharmacology*; D004951:Esterification / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013237:Stereoisomerism
D004852:Epoxy Compounds; D007004:Hypoglycemic Agents; D010169:Palmitic Acids; D019308:Palmitic Acid; C054207:etomoxir