Age-related alteration in signal transduction: involvement of the cAMP cascade

In the present study, we have investigated the involvement of the cAMP signal transduction pathways in young and aged rats. A significantly higher endogenous adenosine 3':5'-cyclic monophosphate (cAMP) level and a significant decline of the adenylate cyclase [AC, ATP pyrophosphate-lyase (cyclizing), EC.4.6.1.1.] activity were observed in striatal tissue from young rats (3 months) in comparison to aged rats (approximately 40 months). In the nucleus accumbens (NA), no age-dependent changes in the cAMP concentration and in the AC basal activity were found. To address the question, whether the interactions of guanine nucleotide-binding protein (G-protein) subunits (G alpha s and Gi) with AC have changed in the aging process, various pharmacological agents that modulate the AC activity (e.g., beta, tau-imidoguanine 5'-triphosphate (GppNHp), sodium fluoride (NaF), forskolin (FSK), and the combinations of GppNHp plus FSK, NaF plus FSK, and NaF plus ethanol (ETOH)) were applied. In addition, a [3H]FSK binding test was carried out. In striatal and NA tissue, the stimulation of the AC activity by FSK was inhibited by GppNHp (via Gi-protein) and was superadditive by the combination of FSK and NaF (via Gs-protein). The absolute AC activity upon stimulation by all agents used was significantly lower in the aged striatum compared to young striatum. In the NA, however, the AC activity showed an age-dependent reduction only upon FSK and upon FSK plus GppNHp stimulation. There was no difference in the specific [3H]FSK binding to the G alpha s protein-coupled catalytic subunit of the AC between young and aged animals both in the striatum and NA.(ABSTRACT TRUNCATED AT 250 WORDS)