Gq/11‐induced intracellular calcium mobilization mediates Per2 acute induction in Rat‐1 fibroblasts

Phase resetting is one of the essential properties of circadian clocks that is required for the adjustment to a particular environment and the induction of Per1 and Per2 clock genes is believed to be a primary molecular event during this process. Although the intracellular signal transduction pathway underlying Per1 gene activation has been well characterized, the mechanisms that control Per2 up‐regulation have not yet been elucidated. In our present study, we demonstrate that Gq/11 coupled receptors mediate serum‐induced immediate rat Per2 (rPer2) transactivation in Rat‐1 fibroblasts via intracellular Ca2+ mobilization. Stimulation of these cells with a high concentration of serum was found to rapidly increase the intracellular Ca2+ levels and strongly up‐regulated rPer2 gene. rPer2 induction by serum stimulation was abrogated by intracellular Ca2+ chelation and depletion of intracellular Ca2+ store, which suggests that the calcium mobilization is necessary for the up‐regulation of rPer2 gene. In addition, suppression of Gq/11 function was observed to inhibit both Ca2+ mobilization and rPer2 induction. Further, we demonstrated that endothelin‐induced acute rPer2 transactivation via Gq/11‐coupled endothelin receptors is also suppressed by a Gq/11 specific inhibitor. These findings together suggest that serum and endothelin utilize a common Gq/11‐PLC mediated pathway for the transactivation of rPer2, which involves the mobilization of calcium from the intracellular calcium store.