INOSITOL 1,4,5-TRISPHOSPHATE ARM OF THE PHOSPHATIDYLINOSITIDE SIGNAL-TRANSDUCTION PATHWAY IN THE RAT CEREBELLUM DURING AGING

To determine whether the intracellular calcium-mobilizing second messenger, inositol 1,4,5-trisphosphate (InsP(3)) and its receptor (InsP(3)R) display age-dependent coordinate regulation, InsP(3), content and [H-3]InsP(3)-binding characteristics were investigated in cerebellar particulate membranes prepared from male Fischer 344 rats at 3, 12 and 25 months of age. Cerebellar InsP(3) content was significantly increased in 25-month-old rats compared with 3-month-old animals. Cerebellar InsP(3)R densities were significantly reduced at 12 and 25 months of age but InsP(3)-binding affinity was significantly decreased only in the 25-month-old animals. The present data strongly suggest that modulation of the phosphoinositide second messenger system may contribute to impaired neuronal responsiveness associated with the aging process in the cerebellum.