Findings Offer Clues to Caffeine's Long-Lasting Kick

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Findings Offer Clues to Caffeine's Long-Lasting Kick
Wed Aug 14, 5:30 PM ET
By Alison McCook

NEW YORK (Reuters Health) - A group of researchers have uncovered evidence for why caffeine's stimulating effects stay with us long after we down the day's last cup of coffee. They have also identified a protein that appears to play a key role in how caffeine exerts its long-lasting effect.



Dr. Gilberto Fisone of the Karolinska Institute in Stockholm, Sweden, and his colleagues found that mice genetically engineered to lack the protein, dubbed DARPP-32, did not experience as long a period of stimulation from caffeine as other mice.

Fisone told Reuters Health that DARPP-32 may therefore represent the means by which one cup of coffee can perk people up for more than the few minutes it takes to drink it down.

"We have found a mechanism, a molecule, which mediates the ability of coffee to cause a prolonged stimulant effect," Fisone said.

Fisone noted that some people believe themselves to be addicted to caffeine, and understanding more about how the substance acts on the body may help explain why they get hooked. Other substances of abuse--including cocaine and amphetamines--also interact with DARPP-32, the researcher added, increasing the possibility that this protein plays an important role in the development of addiction.

Previous research has shown that coffee helps stimulate the body by blocking receptors that would otherwise be activated by adenosine, a chemical that has depressant effects. In the study, published in this week's issue of the journal Nature, Fisone and his team show that blocking the adenosine receptors sets off a chain of chemical reactions, part of which includes activating the DARPP-32 protein.

Once activated, the protein then helps to amplify the effects of caffeine on the body, the researchers demonstrate, enabling caffeine's initial stimulating effect--produced by blocking adenosine receptors--to last for a few hours.

In the current study, Fisone and his colleagues developed their theories based on studies with mice, in which some were engineered to produce no DARPP-32. When these mice were given caffeine, they initially responded to the stimulant, but the effect was much more short-lived than that seen in mice with normal amounts of the protein.

In an interview with Reuters Health, Fisone explained that these results might help explain variations in how people respond to caffeine. While he said he is not aware of people who, like the mice used in this study, do not produce DARPP-32 naturally, Fisone said that individuals are more or less sensitive to caffeine, and the interaction between the substance and DARPP-32 could be a factor.

"The ability of a person to respond more or less to caffeine could depend on this (process)," he said.

Over time, habitual coffee drinkers can also develop a "tolerance" for caffeine, Fisone added, after which a cup of coffee will have less of an effect on them than on first-time drinkers. Again, he suggested DARPP-32 may play a role in this change in response to caffeine over time.

Furthermore, Fisone noted that caffeine also blocks receptors present in a group of nerve cells involved in neurodegenerative disorders such as Parkinson's disease ( news - web sites). This condition is marked by the loss of brain cells that produce the chemical dopamine, resulting in a variety of physical symptoms such as tremor, rigidity and stiffness. Other researchers have shown that caffeine can make it more difficult for these nerve cells to degenerate, perhaps keeping dopamine available to the brain.

The more researchers understand about caffeine, Fisone said, the more likely they may be able to use the substance to help patients with Parkinson's and similar disorders.

"It's important to know about the molecular mechanisms by which substances such as caffeine work," he said.

SOURCE: Nature 2002;418:734-736, 774-778.

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