Characterization of a translational inhibitor isolated from rabbit brain following intravenous administration of d-lysergic acid diethylamide.
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.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry; D002474:Cell-Free System; D002845:Chromatography; D015852:Eukaryotic Initiation Factor-2; D006160:Guanosine Triphosphate / Q000378:metabolism; D007700:Kinetics; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D046911:Macromolecular Substances; D008297:Male; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects; D010448:Peptide Initiation Factors / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D012358:RNA, Transfer, Met; D011817:Rabbits
D015852:Eukaryotic Initiation Factor-2; D046911:Macromolecular Substances; D010448:Peptide Initiation Factors; D011506:Proteins; D012346:RNA, Transfer, Amino Acyl; D012358:RNA, Transfer, Met; C024988:tRNA, formylmethionine-; D006160:Guanosine Triphosphate; D008238:Lysergic Acid Diethylamide