Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. STKE, 20 August 2002
Vol. 2002, Issue 146, p. tw303
[DOI: 10.1126/stke.2002.146.tw303]


Neurobehavior Coffee, Caffeine, and DARPP-32

Caffeine is a well-known psychostimulant that increases motor activity by inhibiting the action of the neuromodulator adenosine. By binding to adenosine receptors (A1 and A2A) present in inhibitory neurons in the brain, caffeine prevents activated A2A receptors from initiating a signaling pathway that triggers cAMP production and protein kinase A (PKA) activation. Lindskog et al. report the behavioral effects of caffeine are no longer observed in mice lacking the cytosolic protein DARPP-32. This is because caffeine increases the phosphorylation of DARPP-32 on a specific threonine residue. By blocking the cAMP-PKA pathway, caffeine decreases the action of the protein phosphatase 2A on DARPP-32. Phosphorylated DARPP-32 can then further inhibit PKA activity, amplifying the shutdown of the cAMP-PKA pathway. The effect likely includes a lower level of phosphorylated target proteins of PKA that regulate nerve activity.

M. Lindskog, P. Svenningsson, L. Pozzi, Y. Kim, A. A. Fienberg, J. A. Bibb B. B. Fredholm, A. C. Nairn, P. Greengard, G. Fisone, Involvement of DARPP-32 phosphorylation in the stimulant action of caffeine. Nature 418, 774-778 (2002). [Online Journal]

Citation: Coffee, Caffeine, and DARPP-32. Sci. STKE 2002, tw303 (2002).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882