Peering at the molecular machinery of the human body, researchers have determined that fragments of cocaine alter critical proteins, even when the drug is no longer detectable in the bloodstream. This newly revealed chemical activity may explain some of cocaine's long-lasting and insidious effects.
Although cocaine stays in the blood for less than an hour, its ill effects can linger. Some people who've ceased using cocaine may suffer persistent inflamed blood vessels and other autoimmune conditions. Yet researchers don't understand how cocaine causes these long-term ailments. Previously, organic chemist Donald Landry of Columbia University in New York City and his colleagues had studied how cocaine breaks down in water. The work led him to suspect that in the body, the drug might break down by attaching a piece of itself to proteins.
Landry's group investigated further. First, the scientists showed that a fragment of cocaine can bind to albumin, a protein abundant in blood and one responsible for shuttling other proteins around. The team then tested which of 21 amino acids--the building blocks of proteins--could bind with cocaine. Only one, called lysine, fit the bill. Because lysine is part of numerous proteins throughout the body, the finding suggests that cocaine has the potential to modify many proteins, not only albumin.
The team then took blood samples from 13 cocaine users who said they hadn't used the drug for at least a day. In six, they looked for cocaine-modified proteins and found two: albumin and macroglobulin. In the other seven, they looked for antibodies to cocaine-modified protein and found such antibodies in two volunteers. The results suggest that cocaine not only alters proteins but transforms them into targets subject to attack by immune cells. The work is reported in the 12 March online early edition of the Proceedings of the National Academy of Sciences. While it remains to be seen where else in the body the proteins are modified and how long they stick around, Landry says the finding "adds one more wrinkle to the possible long-term effects of cocaine."
Although the research doesn't explain the health problems experienced by cocaine users, "it raises the possibility of altered protein function," says Patricia Molina, a molecular pathologist at Louisiana State University Medical Center. "This could lead to further understanding of the tissue-toxic effects of cocaine."