Cyclic changes in cAMP concentration and phosphodiesterase activity in a mammalian circadian clock studied in vitro

Abstract

The mammalian suprachiasmatic nuclei (SCN) contain a circadian pacemaker that continues to keep 24-h time when isolated in vitro. We are investigating the role of cAMP in the cellular mechanisms underlying SCN function. We have previously shown that increasing intracellular cAMP during the subjective day resets the SCN pacemaker in the in vitro rat brain slice preparation. We now report that the level of cAMP fluctuates within the rat SCN under constant conditions in vitro. The level of endogenous cAMP is high during late day and late night, and low during early night. These changes in cAMP concentration are accompanied by opposite changes in phosphodiesterase activity; we detected no significant change in adenylate cyclase activity. These results provide further support for the hypothesis that cAMP is involved in circadian function in the SCN.