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 (InsP3) and its receptor (InsP3R) display age-dependent coordinate regulation, InsP3 content and [3H]InsP3-binding characteristics were investigated in cerebellar particulate membranes prepared from male Fischer 344 rats at 3, 12 and 25 months of age. Cerebellar InsP3 content was significantly increased in 25-month-old rats compared with 3-month-old animals. Cerebellar InsP3R densities were significantly reduced at 12 and 25 months of age but InsP3-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.