Caffeine hit enigma solved

A protein that intensifies and prolongs caffeine`s kick is identified in this week`s issue of the science journal Nature.​

Although caffeine is probably the world's most widely used psychostimulant, surprisingly little is known about its molecular mechanism, the journal reports. At concentrations equivalent to a few cups of coffee a day, it binds and blocks nerve cells that normally inhibit voluntary movements in the brain`s movement centre, the striatum.

Gilberto Fisone of the Karolinska Institute, Stockholm, Sweden, and colleagues found that a protein called DARPP-32 is the key to the action of coffee: mice genetically engineered to lack DARPP-32 are immune to some of its stimulatory effects.

Low doses of caffeine appear to trigger a positive feedback loop in striatal nerves: they subdue a protein called protein kinase A, which in turn keeps DARPP-32 phosphorylated. In this form, it dampens protein kinase A further. Together with other molecules in the feedback loop, they control the activity of further proteins that inhibit nerve activity, and thus keep us hyperactive.

"DARPP-32 keeps us going until the next coffee break by extending the effects of the last cup,"​ wrote Jean-Marie Vaugeois of the University of Rouen, France, in this week's issue of Nature​.

Further information about the study can be obtained from Gilberto Fisone: gilberto.fisone@neuro.ki.se.