Decreased efficacy of inositol 1,4,5-trisphosphate to elicit calcium mobilization from cerebrocortical microsomes of aged rats.

The effects of aging on the ability of brain microsomes to sequester calcium in response to ATP stimulation and to release calcium in response to inositol 1,4,5-trisphosphate (IP3) stimulation were examined. Calcium uptake and release were compared in microsomal preparations from the cerebral cortex, hippocampus, thalamus, and cerebellum of 3-, 16-, and 28-month-old male Fischer 344 rats. No age-related differences were found in the ability of brain microsomes to sequester calcium in response to ATP stimulation. A maximally effective concentration of IP3 (1 microM) released approximately 30% of the calcium sequestered by microsomes. This was observed in all brain regions and age groups studied except in the cerebral cortex, where the amount of calcium released by IP3 was reduced by 50% in the oldest age group. Concentration-response curves for IP3 in this brain region from 3- and 28-month-old rats confirmed that the maximally effective concentrations, the EC50 values, and the Hill coefficients did not differ with aging. These data indicate that the efficacy of IP3 is selectively diminished in the cerebral cortex of aged rats and that this age-related change may contribute to the attenuated responsiveness of neurons in this brain region to activation by phosphoinositide-coupled receptors.