Effects of 2-tetradecylglycidic acid on rat platelet energy metabolism and aggregation.
We investigated the role of energy supplied by long-chain fatty acid oxidation in rat platelet function. Inhibition of the mitochondrial uptake of long-chain fatty acids was achieved by treating rats with 2-tetradecylglycidic acid (TDGA), a potent inhibitor of the overt form of carnitine palmitoyltransferase (CPT-I). The maximum aggregation rate (MAR), CPT-I activity, lactate production, oxygen consumption and adenine nucleotide content of isolated rat platelets were then studied in vitro. 4 h after the in vivo administration of TDGA, the CPT-I activity in saponin-permeabilized platelets was nearly completely inhibited along with a significant reduction in the MAR induced by ADP, thrombin and ionophore A23187. The ATP level, adenylate energy charge (ATP + 1/2 ADP)/(ATP + ADP + AMP) and ATP/ADP ratio in the platelet cytoplasmic pool were also reduced. Platelets from TDGA-treated rats showed lower oxygen consumption rates in both the basal respiratory and oxygen burst states. These results indicate that mitochondrial long-chain fatty acid oxidation coupled to oxidative phosphorylation is an important energy source in rat platelets and is probably involved in the maintenance of platelet function. Enhanced in vitro lactate production in platelets from TDGA-treated rats may have resulted from a compensatory increase in glycolysis which only partly compensated for impaired long-chain fatty acid oxidation.
Ishikura
H
H
Department of Emergency and Critical Care Medicine, Kansai Medical University, Osaka, Japan.
Takeyama
N
N
Tanaka
T
T
D000227:Adenine Nucleotides / Q000032:analysis; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D003593:Cytoplasm / Q000378:metabolism; D004734:Energy Metabolism; D004852:Epoxy Compounds / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000494:pharmacology
D000227:Adenine Nucleotides; D004852:Epoxy Compounds; D005227:Fatty Acids; D007773:Lactates; D010975:Platelet Aggregation Inhibitors; D000001:Calcimycin; D000244:Adenosine Diphosphate; D002334:Carnitine O-Palmitoyltransferase; D013917:Thrombin; C021756:2-tetradecylglycidic acid