Aging does not alter brain muscarinic receptor-mediated phosphoinositide hydrolysis and its inhibition by phorbol esters, tetrodotoxin and receptor desensitization

The effects of aging on muscarinic receptor-mediated phosphoinositide (PI) hydrolysis in the brain were investigated in Fischer-344 rats. Oxotremorine-M stimulated this response to the same magnitude in young and old rats in the cerebral cortex, striatum, hippocampus, thalamus, hypothalamus and cerebellum, although maximal stimulation varied among brain regions within each age group. The PI response was also equalloy potentiated by elevated K⁺ or suppressed by tetrodotoxin in both age groups. In addition, a phorbol ester attenuated muscarinic receptor-mediated PI hydrolysis in the cerebral cortex to the same extent in young and aged rats. Moreover, preincubation with oxotremorine-M resulted in a similar down-regulation of cell-surface receptors and desensitization of receptor function regardless of age. Therefore, under our experimental conditions, PI hydrolysis in response to activation of brain muscarinic receptors does not appear to be sensitive to aging-related alterations.