Influences of pertussis toxin, guanine nucleotides and forskolin on adenylate cyclase in striatal membranes of infant, adult and senescent rats.

To identify age-related changes in the dopamine (DA) receptors-GTP-binding protein-adenylate cyclase system, the following experiments were performed at 7 days (infant), 70 days (adult) and 2 years (senescent) in striatal membranes of rats: (1) effects of GTP in the presence and absence of pertussis toxin (islet-activating protein, IAP) on adenylate cyclase in the presence of forskolin alone, (2) the same in the presence of forskolin plus DA and (3) the corresponding effect of guanyl-5'-yl-beta, alpha-imido-diphosphate (GppNHp). GTP caused biphasic effects: the activation at 1 microM and the inhibition at 100 microM on forskolin-stimulated cyclase activity at 70 days. The inhibition was suppressed with IAP pretreatment. In infant membranes, 100 microM GTP inhibited the activity in the absence and presence of 100 microM DA and IAP induced a reversal from the inhibition to the stimulation only in the presence of DA. In senescent animals, neither GTP nor IAP affected the activity. GppNHp at 1, 10 and 100 microM only activated and did not inhibit forskolin-stimulated cyclase at each stage. GppNHp-caused stimulation was no more affected by IAP. IAP ADP-ribosylated 41,000 dalton proteins at each stage and the specific activity of ADP-ribosylation was not changed during development and aging. It is suggested that inhibitory GTP-binding protein (Gi) with molecular size of 41,000 dalton is involved in DA receptor-adenylate cyclase system whose function is low at infant stage and markedly decreased at senescent stage in rat striatal membranes.