Changes in lipid composition and isoproterenol- and ethanol-stimulated adenylate cyclase activity in aging Fischer...

In the aging rat bladder dome, changes are noted in membrane composition and in the activity of the membrane-bound enzyme, adenylate cyclase (AC). When bladder domes from 22 day and 22 to 24 month Fischer rats are compared, changes in composition include: a 25% decrease in percentage of protein [(milligrams of protein per milligram of wet weight) x 100]; an approximately 40% decrease in both the total phospholipid content and in the content of the major phospholipids, phosphatidylcholine and phosphatidylethanolamine; and a 69% increase in the cholesterol to phospholipid ratio. These changes are indicative of a more rigid lipid bilayer in the aged rat bladder. Changes in AC with aging include a decrease in basal and forskolin-activated AC and a loss of the ability of isoproterenol to activate AC in the aged (22-24 month) rat bladder dome homogenate. Activation by isoproterenol (ISO; 3 microM) is 55 and 72% over 5' guanylimidodiphosphate [Gpp(NH)p; 1 microM] controls in 22 day and 90 day rat bladder dome homogenates, respectively. Activation by AC by NaF and Gpp(NH)p does not decline with aging. Ethanol, an agent that increases membrane fluidity, stimulates AC to a much greater extent in homogenates from the 22 month than from the 22 day or 90 day rat bladder dome. The ethanol-induced activation occurs not only in basal AC but also in Gpp(NH)p- and ISO-plus Gpp(NH)p-activated AC. The observed changes in AC with aging in part may reflect changes in the membrane lipid environment.