BBB Seminar: Bertil B. Fredholm
Caffeine, adenosine and the brain
Bertil B. Fredholm
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Caffeine is the most widely used of all drugs. The reason is its effects on the central nervous system. In low doses the effects can be explained by blockade of adenosine receptors. There are four such receptors in all mammalian species: A1, A2A, A2B and A3. The first three are potently inhibited by caffeine, but the fourth requires toxic doses. The A1 and A2A receptors show high affinity for adenosine, whereas A2B receptors require higher levels. Such levels are rarely seen in the brain under physiological conditions. Thus caffeine probably acts by blocking CNS A1 and A2A receptors. I will demonstrate how caffeine acts to alert us and wake us up by blocking A2A receptors, and specifically A2A receptors in the nucleus accumbens shell. Activation of both A1 and A2A receptors can induce sleep, but these effects are exerted elsewhere. A2A receptors are also important in other dopaminergic transmission and play a role in Parkinson's disease. A1 receptors regulate transmitter release and are important in reducing epilepsy. Indeed activation of A1 receptor signaling appears to be a way to treat even severe epilepsy. I will also briefly touch upon the effects on pain and the role of the adenosine system in ischemia.
Host: Stein Ove Døskeland , Department of Biomedicine