Characterization of a Translational Inhibitor Isolated from Rabbit Brain Following Intravenous Administration of d‐Lysergic Acid Diethylamide

Abstract

Intravenous administration of d-lysergic acid diethylamide (LSD) to rabbits results in a transient inhibition of brain protein synthesis in vivo and in vitro. A translational inhibitor that appears in the postribosomal supernatant fraction of cerebral hemispheres following LSD administration was partially purified by gel filtration on Sephadex G-150 and precipitation with 60% ammonium sulfate. This inhibitor, which was proteinaceous, reduced the translational capacity of an initiating cell-free protein synthesis system derived from brain. It also inhibited a messenger RNA-dependent reticulocyte lysate programmed with brain polysomes and a globin-synthesizing reticulocyte lysate system. Addition of the partially purified inhibitor to a brain cell-free protein synthesis system resulted in the decreased formation of ternary complexes as well as 40 and 80S initiation complexes, suggesting that the inhibitor affects an early step in the initiation of protein synthesis in brain.

Effects of Amphetamine on Protein Synthesis and Energy Metabolism in Mouse Brain: Role of Drug‐Induced Hyperthermia

“…Recent results suggest that modification of initiation factor 4F may also be involved both in reduced overall translation and selective synthesis of heat shock proteins (Duncan and Hershey, 1984;Panniers et al, 1985;Duncan et al, 1987). It is likely to emerge that similar events occur in brain following drug-induced hyperthermia in vivo (Fleming and Brown, 1986). The apparent induction of the major mammalian stress protein, hsp 70, in brain and liver following amphetamine hyperthermia is consistent with the above view, and with the considerable body of similar results obtained in the rabbit following LSD-induced hyperthermia (Heikkila et al, 1981;Brown, 1983;Cosgrove and Brown, 1983;Brown et al, 1985).…”