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Res Commun Mol Pathol Pharmacol. 1996 Dec;94(3):305-16.

Concentration dependence of the metabolic effects of diltiazem in the isolated perfused rat liver.

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1
Department of Biochemistry, University of Maringá, Brazil.

Abstract

The concentration dependence of the effects of diltiazem on glycogenolysis, glycolysis, gluconeogenesis and oxygen uptake was investigated in the isolated perfused rat liver. The effects of this compound were very complex. At low concentrations diltiazem increased glycolysis, glycogenolysis (up to 200 microM) and oxygen uptake (up to 100 microM) in livers from fed rats. At the concentrations of 500 and 750 microM the drug inhibited glycolysis, glycogenolysis and oxygen uptake. In livers from fasted rats diltiazem inhibited gluconeogenesis from pyruvate. Inhibition was virtually complete at a concentration of 500 microM. Lactate production from pyruvate and oxygen uptake were also inhibited. Several alterations were observed after cessation of the infusion of diltiazem (i.e., a posteriori effects). The most prominent of these effects was an activation of glucose release in livers from fed rats (glycogenolysis), which occurred after cessation of the infusion of 500 or 750 microM diltiazem. It can be concluded that diltiazem is primarily an inhibitor of energy metabolism in the liver. At high concentrations it blocks the respiratory chain. At low concentrations it could be acting as an uncoupler, because inhibition of a biosynthetic process (gluconeogenesis) occurred at concentrations (up to 200 microM) that simultaneously increased oxygen uptake and glycolysis.

PMID:
9029676
[Indexed for MEDLINE]
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