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Adenosine and Sleep

Dateline: 03/13/00

By Alan Bruzel

What Is Adenosine?

Most people have made the acquaintance of adenosine (pronounced uh-DEN-eh-seen) in its phosphorylated form: adenosine triphosphate (ATP). This is the high-energy molecule used to power the contraction of muscle and to fuel anabolic metabolism (the synthesis of complex molecules such as proteins, nucleic acids, fats, and polysaccharides). In its non-phosphorylated form, adenosine plays a role in regulating sleep.

How Does Adenosine Affect Sleep?

During sleep deprivation, brain levels of adenosine increase. Many organs (brain, heart, and kidney, for example) contain adenosine receptors. These are protein molecules located on the cell surface that specifically bind adenosine. Binding of adenosine to these specific receptors on brain neurons – a situation occurring more readily when adenosine concentrations are high – leads to reduced neuronal activity, and a tendency of the organism to fall asleep.

Molecules That Mimic Adenosine

Using adenosine, itself, as a sleep-inducing agent is complicated by the fact that it depresses heart rate and lowers blood pressure. Adenosine analogs used as therapeutic agents to encourage sleep must therefore be designed to bind brain adenosine receptors only (not adenosine receptors in the heart), and, because there are four subtypes of adenosine receptor, must show a preference for only the subtype(s) responsible for the sleep effect. These compounds are not yet on the market. However, a substance that blocks the binding of adenosine to its receptor, and which thus prevents adenosine's sleep-inducing effect, is on the market and has been swallowed for thousands of years in the form of caffeine – a molecule structurally related to adenosine.

Adenosine	Caffeine

What the Web Has to Say about:
Adenosine and Sleep

Adenosine and Sleep
Sleep research theories assessing adenosine's actions. From Society for Neuroscience.

Adenosine and Sleep
Historical background of adenosine's sleep effect. From Miodrag. Radulovacki, University of Illinois at Chicago.

Adenosine in Sleep and Wakefulness
Abstract by T. Porkka-Heiskanen, University of Helsinki, demonstrates adenosine accumulation increases sleep propensity.

Awakening to How We Sleep
Mechanisms believed to trigger sleep. Article by William J. Cromie, Harvard University Gazette.

Brain Chemical That Causes "Cat Naps" Found
Discussion of sleep studies in cats. Associated Press article by Paul Recer.

Chemical and Neuronal Mechanisms of Sleep
Neurotransmitters and their sleep effects. A chapter from Basics of Sleep Behavior.

Does Sleep Recharge the Brain?
Adenosine, sleep, and future research directions. Article by Craig Heller and Joel Benington, Stanford University.

Is Adenosine a Key Feedback Molecule in Homeostatic Regulation of Sleep?
Studies of sleep-promoting activity of adenosine. From Joel H. Benington and H. Craig Heller, Stanford University.

Mind Travelers: Night Moves
Results of sleep studies on humans and animals. Article by Bob Holmes, New Scientist.

Napless Cats Awaken Interest in Adenosine
Thoughts on why the brain uses adenosine to regulate sleep. From J. Travis, Science News Online.

Scientists Awake to Treatment for Sleep Apnea
Animal studies show adenosine reduces incidents of apnea. Article by Amanda Mazur, UICNEWS.

Specific Ligands for the Adenosine Receptor Family
Studying physiological role of adenosine receptors using analog molecules. Article by Kenneth A. Jacobson in Neurotransmissions.

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