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Voss EW, Winkelhake JL. 
“Mechanism of Lysergic Acid Diethylamide Interference with Rabbit Antibody Biosynthesis.”. 
Proc Natl Acad Sci. 1974;71(4):1061-1064.
The mechanism of lysergic acid diethylamide (LSD) interference with rabbit immunoglobulin;bio-synthesis was investigated. Lymphoid cells were harvested from rabbits hyperimmunized with fluorescein conjugated gamma globu,lin:(IgG).and boosted by hapten administiation 5-6 days prior to cell harvest. The cells were incubated for 18 hr at 57 ° in minimal medium lacking lèucine,but supplementéd with 3H-leucine (A), in minimal medium 1acking leucine but supplemented with 3H-leucine -(A), in minimal medium lacking leucine and tryptophan but, supplemented with 3H-leucine -and 14C-tryptophan (B) ,or in B with added LSD. The labeled extracellular supernatant-from reaction mixture A contained 202x103 cpm/0.1 mL cells. The supernatant from mixture B contained 212x10^3 cpm/0.1 ml -cells and the ratio of 3H-leucine to-l4C-tryptophan was 3.9. In the presence of 10,-1.0 and'0'.01mcg/ml LSD supernatants contained l40, 171 and 199x10^3 cpm/0'.1 ml cells and the 3H/14C ratios were 10.7, 7.1, and 5.'3, respectively. In the presence of 10.0mcg/ml LSD plus 100 mcg/ml tryptophan, the supernatant contained 209x103 cpm/0.1 ml cells and the ratio was 4.5. Total extracellular 3H incorporated in reactionsB and C was equal, the increased ratio in C being',:therefore; due to a decrease in tryptophan incorporation. Addition of unlabeled tryptophan reversed the ratio changes. Sucrose gradient analysis: revealed that 1abeled protein from reaction-C-was of lower molecular weight than that from reaction-B or than-rabbit IgG-control. The low-molecular weight product was not precipitable by goat anti- rabbit IgG, anti-H chain:or anti-L chain antisera. Increasing levels of LSD decreased precipitability of the protein product in 50% ammonium sulphate. In the presence of l0 mcg/ml LSD plus 100 mcg tryptophan, 800f ths material was ammonium suiphate precipitable. On isoelectric focusing,:material from reaction C gave 2 peaks with pIs- of 4.9 and 5.2. - The IgG control and material from B had a pI of 7.0. The effect of LSD on immunoglobulin biosynthesis resembles that of an amino acid analog.
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