Covalent modification of proteins by cocaine.
Cocaine covalently modifies proteins through a reaction in which the methyl ester of cocaine acylates the epsilon-amino group of lysine residues. This reaction is highly specific in vitro, because no other amino acid reacts with cocaine, and only cocaine's methyl ester reacts with the lysine side chain. Covalently modified proteins were present in the plasma of rats and human subjects chronically exposed to cocaine. Modified endogenous proteins are immunogenic, and specific antibodies were elicited in mouse and detected in the plasma of human subjects. Covalent modification of proteins could explain cocaine's autoimmune effects and provide a new biochemical approach to cocaine's long-term actions.
Deng
Shi-Xian
SX
Department of Medicine, Division of Clinical Pharmacology and Experimental Therapeutics, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Bharat
Narine
N
Fischman
Marian C
MC
Landry
Donald W
DW
D000215:Acylation / Q000187:drug effects; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000097:blood / Q000150:complications / Q000276:immunology; D015374:Biosensing Techniques; D015153:Blotting, Western; D003042:Cocaine / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000097:blood / Q000150:complications / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*
D001323:Autoantibodies; D001324:Autoantigens; D007106:Immune Sera; D012709:Serum Albumin; D003042:Cocaine; D008239:Lysine