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

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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 80 S initiation complexes, suggesting that the inhibitor affects an early step in the initiation of protein synthesis in brain.