DIFFERENTIAL-EFFECTS OF SERUM PROTEIN(S) ON SUBSTRATE OXIDATION BY ISOLATED SYNAPTOSOMES AND CULTURED RAT-BRAIN ASTROCYTES

This report extends the finding that serum protein(s) (0.5 mg/ml) caus ed a 50% decrease in the rate of glucose oxidation by dissociated brai n cells with only marginal effects on the oxidation of other substrate s. Since dissociated cells represent a heterogeneous population, studi es were initiated to determine the effect of serum on the rates of sub strate oxidation by isolated synaptosomes and cultured rat brain astro cytes. Experiments revealed that the addition of 5% serum v/v to the r eaction mixture resulted in a decrease in the rate of (CO2)-C-14 produ ction from [6-C-14]glucose by isolated synaptosomes by more than 70%. In contrast, the addition of 5% serum had little or no effect on the ( CO2)-C-14 production from [U-C-14]glutamine by the synaptosomes and on ly marginal effects (20-25%) on (CO2)-C-14 production from [U-C-14]lac tate and 3-hydroxy[3-C-14]butyrate. The effect of serum on the rates o f substrate oxidation were similar for synaptosomal preparations obtai ned from adult animal brains or 18-day-old rats, except that with the latter preparation, (CO2)-C-14 production from 3-hydroxy[3-C-14]butyra te was more attenuated by the presence of serum than with the former s ynaptosomal preparation (50 vs. 25%). In contrast to the results with synaptosomes, the presence of 5% serum enhanced the rates of (CO2)-C-1 4 production from [6-C-14]glucose, 3-hydroxy[3-C-14]butyrate and [U-C- 14]lactate by 61, 35 and 69%, respectively, in cultured rat brain astr ocytes. However, this enhancement did not occur when the cells were gr own in chemically defined media or when dibutyryl cAMP was added to th e media. Collectively the results suggest that the presence of serum p rotein(s) may contribute to the regulation of substrate oxidation by b rain cells in a yet to be defined manner; either by acting directly wi th enzymes in the metabolic pathway or via an interim (second messenge r) factor.