Metabolic sites of action of halothane in rat atria

Abstract

Rat atrial metabolism was monitored by measuring the production of 14CO 2 from 14C-labeled substrates. D-Glucose and D-mannose metabolism were depressed by low concentrations of halothane (1 mM) which did not significantly affect the metabolism of pyruvate, D-fructose, DL-beta-hydroxybutyrate or octanoate. Halothane (1 mM) did not alter the uptake of 3- O-methyl glucose by rat atria. It is concluded that halothane blocks an early step(s) in glycolysis. The most likely sites are the phosphoglucose isomerase (PGI) and phosphomannose isomerase (PMI) steps. The incorporation of D-glucose, D-mannose and D-fructose into glycogen were significantly inhibited by 1 mM halothane, although the total glycogen content was not affected. We conclude that halothane inhibits glycogen turnover. Higher concentrations of halothane (8 and 16 mM) required to inhibit the metabolism of pyruvate and D-fructose. This action of halothane is attributed to the known inhibition by halothane of electron transport processes. Neither DL-beta-hydroxybutyrate nor octanoate metabolism to CO 2 was affected by 1 mM halothane, although higher concentrations of halothane produced an inhibition. It is concluded that some of the steps in fatty acid oxidation are unaffected by low concentrations of halothane.