ALTERATIONS OF ADENYLYL CYCLASE-LINKED G-PROTEINS IN RAT-LIVER DURINGAGING

beta-Adrenergic stimulation of adenylyl cyclase in rat liver increases during aging. We examined whether this increase is related to alterat ions in the stimulatory and inhibitory G proteins (G(s) and G(i)) link ed to adenylyl cyclase. Levels of immunoreactive alpha- and beta-subun its of G(s) and G(i) in liver plasma membranes from 6-, 12-, 18-, and 24-mo-old rats were unchanged with age, as was pertussis toxin-catalyz ed [P-32]ADP ribosylation of G(i) alpha. Cholera toxin-catalyzed [P-32 ]ADP ribosylation of G(s) alpha and G(s) bioactivity, assessed as reco nstitution of adenylyl cyclase activity in S49 cyc(-) cell membranes, increased two- to threefold between 6 and 12-18 mo, and declined by 24 mo. Recombinant ADP ribosylation factor (ARF) enhanced cholera toxin labeling of G(s) alpha at all ages, yet abolished the increase in toxi n labeling at 12-18 mo. Auto-ADP ribosylation of the cholera toxin A(1 ) peptide also increased transiently with age. Alteration of G(s) alph a, as reflected by increased cholera toxin labeling and G(s) bioactivi ty, may be involved in the regulation of beta-adrenergic-responsive ad enylyl cyclase in rat liver during aging. Moreover, changes in endogen ous ARF levels could contribute to age differences in cholera toxin la beling of G(s) alpha.