Age-related changes in receptor-mediated and depolarization-induced phosphatidylinositol turnover in mouse brain.

The effect of aging on receptor- and G-protein-activated and on depolarization-induced phosphoinositide (PI) hydrolysis was examined in mechanically dissociated neurons from female NMRI mice. Additionally, age-dependent changes in Ca2+ homeostasis, i.e. changes in basal intracellular calcium ([Ca2+]i) and in depolarization-induced rise in [Ca2+]i were investigated. No age-related differences in PI hydrolysis were found after stimulation of muscarinic cholinergic, alpha 1, serotonin and quisqualate receptors coupled to the phosphoinositide-phospholipase C (PI-PLC) system. PI hydrolysis following stimulation with AMPA ((RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) revealed a significantly increased response in aged animals. Activation of G-proteins with NaF also induced a higher inositol monophosphate (InsP1) accumulation in aged mice. Moreover, InsP1 accumulation due to PLC activation by increased [Ca2+]i after depolarization with KCl was significantly increased in neurons from aged animals. Investigations about age-related changes in Ca2+ homeostasis revealed lower basal [Ca2+]i and lower rise in [Ca2+]i after depolarization with KCl. The data indicate that receptor-mediated and depolarization-induced PI hydrolysis are differentially affected by aging. Decreased availability of [Ca2+]i in aged animals may enhance the sensitivity of Ca(2+)-activated mechanisms. This may explain increased KCl- and AMPA-induced InsP1 accumulation whereas receptor-coupled PLC activation is less affected.