Age-related alteration in the catecholamine-sensitive adenylate cyclase system of the rat cerebral cortex

Reduced adenylate cyclase (AC) activity of cerebral cortical membrane in the presence of guanine-nucleotide analog [Gpp(NH)p] was observed in 12-month-old rats (aged rats) compared with 2-month-old rats (controls). The EC50 value for Gpp(NH)p activation to AC was slightly but significantly increased in aged rats and the half time for maximal activation of AC by Gpp(NH)p, either with or without isoproterenol was also longer in aged rats. Digitonin-solubilized AC catalytic moiety had a lower activity in the aged rats than in controls. The 125I-pindolol binding to beta-receptor in the cortical membrane from aged rats was decreased. GTP increased the Hill coefficient for isoproterenol displacement binding in controls, but such a change was not noted in aged rats. However, the percent increase of AC activity by 1 microM isoproterenol was greater in aged rats than that in controls. Furthermore, the EC50 value for isoproterenol stimulation of AC in control was lower compared with aged rats. Our results indicate that the decreased AC activity in aged rats may be due to a reduced receptor density, functional changes in GTP-binding protein (G protein) activity, and a reduced catalytic subunit activity. Compensatory changes in the beta receptor-G protein-AC coupling system may also occur during aging.