Involvement of DARPP-32 phosphorylation in the stimulant action of caffeine

Maria Lindskog, Per Svenningsson, Laura Pozzi, Yong Kim, Allen A. Fienberg, James A. Bibb, Bertil B. Fredholm, Angus C. Nairn, Paul Greengard and Gilberto Fisone ()
Additional contact information
Maria Lindskog: Karolinska Institutet
Per Svenningsson: The Rockefeller University
Laura Pozzi: Karolinska Institutet
Yong Kim: The Rockefeller University
Allen A. Fienberg: The Rockefeller University
James A. Bibb: The Rockefeller University
Bertil B. Fredholm: Karolinska Institutet
Angus C. Nairn: The Rockefeller University
Paul Greengard: The Rockefeller University
Gilberto Fisone: Karolinska Institutet

Nature, 2002, vol. 418, issue 6899, 774-778

Abstract: Abstract Caffeine has been imbibed since ancient times in tea and coffee, and more recently in colas. Caffeine owes its psychostimulant action to a blockade of adenosine A2A receptors1, but little is known about its intracellular mechanism of action. Here we show that the stimulatory effect of caffeine on motor activity in mice was greatly reduced following genetic deletion of DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000)2. Results virtually identical to those seen with caffeine were obtained with the selective A2A antagonist SCH 58261. The depressant effect of the A2A receptor agonist, CGS 21680, on motor activity was also greatly attenuated in DARPP-32 knockout mice. In support of a role for DARPP-32 in the action of caffeine, we found that, in striata of intact mice, caffeine increased the state of phosphorylation of DARPP-32 at Thr 75. Caffeine increased Thr 75 phosphorylation through inhibition of PP-2A-catalysed dephosphorylation, rather than through stimulation of cyclin-dependent kinase 5 (Cdk5)-catalysed phosphorylation, of this residue. Together, these studies demonstrate the involvement of DARPP-32 and its phosphorylation/dephosphorylation in the stimulant action of caffeine.

Date: 2002
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature00817 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:418:y:2002:i:6899:d:10.1038_nature00817

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature00817

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().