Studies on the mechanism of covalent incorporation of a lysergyl derivative to immunoglobulin peptides in vitro.
In vitro incubation of hyperimmune rabbit lymphoid cells with the hallucinogenic indole alkaloid, d-lysergic acid diethylamide (LSD), results in biosynthesis of modified, secretable immunoglobulin peptides. Modification involves covalent attachment of the lysergyl moiety to COOH-terminal portions of the peptides. Aalogous effects occur when cells are incubated in vitro in the presence of the non-hallucinogenic LSD analogue, d-lysergic acid, and N-[3H]-carboxymethyl-d-lysergamide. The phenomenon is reversed by tryptophan and is inhibited by puromycin and cycloheximide. In vitro attachment of the lysergyl moiety occurs in the presence of actinomycin D at levels which inhibit RNA synthesis. While LSD is not attached to intracellular tRNA, the drug binds to 80 S ribosomes from hyperimmune lymphoid cells with high affinity (K A equals 3.5 times 10-8 M-1). Similar binding occurs to nonimmune splenic ribosomes. Implications of these findings are discussed with respect to the degree of involvement of cellular protein translational mechanisms in the covalent attachment of the lysergyl moiety to low molecular weight immunoglobulin peptides.
D000818:Animals; D001665:Binding Sites; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D007128:Immunoglobulin Fragments; D007136:Immunoglobulins / Q000096:biosynthesis*; D008214:Lymphocytes / Q000378:metabolism; D008237:Lysergic Acid / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008861:Microsomes / Q000378:metabolism; D011691:Puromycin / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D012343:RNA, Transfer / Q000378:metabolism; D011817:Rabbits; D012270:Ribosomes / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
D007128:Immunoglobulin Fragments; D007136:Immunoglobulins; D003609:Dactinomycin; D011691:Puromycin; D012313:RNA; D014364:Tryptophan; D008238:Lysergic Acid Diethylamide; D012343:RNA, Transfer; D003513:Cycloheximide; D008237:Lysergic Acid