Selective effects of LSD and hyperthermia on the synthesis of synaptic proteins and glycoproteins.

Protein synthesis in rabbit brain was inhibited following the intravenous injection of LSD. The incorporation of [35S]methionine into brain microsomal and synaptic fractions was decreased by 35-45% relative to control values. A selective increase was observed, however, in the relative labeling of a protein of molecular weight 75,000. Our previous studies have shown that LSD induces an increase in body temperature (i.e. hyperthermia) in rabbits. When LSD-induced hyperthermia was blocked the general reduction in labeling of microsomal and synaptic proteins was still apparent but the selective increase in relative labeling of the 75,000 dalton protein was not. Induction of hyperthermia by means other than LSD (i.e. elevation of ambient temperature) produced selective increases in the relative labeling of microsomal and synaptic proteins of molecular weight 75,000 and 95,000. These proteins are similar in molecular weight of two of the major 'heat shock' proteins whose synthesis is induced in several cultured cell lines following elevation of ambient temperature. Fractionation of [35S]methionine-labeled synaptic membranes by lectin affinity chromatography and analysis of [3H]fucose labeling patterns indicated that, in contrast to the general reduction in labeling of brain proteins, the synthesis of synaptic glycoproteins was not altered by LSD. The synthesis of glycosylated proteins present in other subcellular fractions was, however, reduced. These results suggest that LSD induced selective changes in the synthesis of brain proteins and that the synthesis of synaptic glycoproteins may be relatively resistant to drug administration.