Metabolic effects of trifluoperazine in the liver and the influence of calcium.
The effects of trifluoperazine on hepatic cell metabolism were investigated using isolated perfused rat liver. The following effects of trifluoperazine were found: (1) trifluoperazine inhibited oxygen uptake, the site of action being the mitochondria. Half-maximal inhibition occurred at concentrations around 50 microM; with 100 microM trifluoperazine the effect was already maximal. When Ca2+ was withdrawn from the perfusion medium and the intracellular Ca2+ pools were exhausted, the inhibitory action on respiration was no longer observable. The reintroduction of Ca2+ restored inhibition. (2) Glycogenolysis and glycolysis were not significantly affected during the infusion of trifluoperazine. After stopping trifluoperazine infusion, however, glycogenolysis (glucose release) experienced a transitory stimulation. (3) Gluconeogenesis from lactate as the carbon source was inhibited by trifluoperazine. This inhibition was approximately proportional to the inhibition of oxygen uptake. Withdrawal of Ca2+ diminished, but it did not eliminate, inhibition of gluconeogenesis. (4) Ketogenesis was also inhibited in parallel with the inhibition of oxygen uptake. Withdrawal of Ca2+ from the perfusion fluid also abolished this action. (5) The effects of trifluoperazine were reverted very slowly when its infusion was stopped. The recovery of oxygen uptake at 50 min after cessation of the infusion was only 30%. Uptake of the substance was very fast. Absence of Ca2+ did not affect uptake. It was concluded that inhibition of mitochondrial energy metabolism is one of the most prominent effects of trifluoperazine in the liver. The fact that this inhibition depends on Ca2+ is unique.
Hübler
M O
MO
Department of Biochemistry, University of Maringá, Brazil.
Ishii-Iwamoto
E L
EL
Pagadigorria
C
C
Bracht
A
A
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000633:toxicity*; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D007657:Ketone Bodies / Q000096:biosynthesis; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014268:Trifluoperazine / Q000633:toxicity*
D018492:Dopamine Antagonists; D007657:Ketone Bodies; D007773:Lactates; D014268:Trifluoperazine; D019344:Lactic Acid; D006003:Glycogen; D005947:Glucose; D010100:Oxygen; D002118:Calcium