Membrane viscosity correlates with alpha 1-adrenergic signal transduction of the aged rat cerebral cortex.

We investigated, using adult (2-month-old) and senescent (12- and 24-month-old) rats, the effects of aging on the relationship between the alpha 1-adrenergic coupling system and the membrane viscosity of the cerebral cortex. There was no age-related difference in the KD values of [3H]prazosin binding on the membranes. The Bmax values of [3H]prazosin binding were reduced with advanced age. Norepinephrine-induced formation of 3H-labeled inositol phosphates (3H-IPs) in the slices increased with advanced age. The EC50 values for norepinephrine to stimulate the formation of 3H-IPs at advanced age were lower than that at adult age. The cholesterol content in membranes increased with advanced age. No changes in the phospholipid content in membranes were observed with advanced age. Concomitantly, an increase of the molar ratio of cholesterol to phospholipids was observed with advanced age. The membrane viscosity as measured by 1,6-diphenyl-1,3,5-hexatriene increased with advanced age. These results indicate that the altered cholesterol content and/or viscosity in cortical membranes of the aged rat may account for the loss of alpha 1-adrenergic receptor density and/or compensatory changes in the receptor-phospholipase C coupling system.