Relationship between the inhibition of adenylate cyclase by pentobarbital and the functional coupling of Ns and the catalytic unit.

The effect of barbiturate on adenylate cyclase system was examined in rat brain. Pentobarbital inhibited the enzyme activities in both synaptic membrane and solubilized catalytic unit of the system in dose and time-dependent manners. The inhibitory effect of pentobarbital was more potent on the activation of the system by NaF-AlCl3 than on the basal activity. The inhibitory effect, however, was less in the synaptic membrane in which the catalytic unit was prestimulated through coupling with Ns by the treatment with NaF-AlCl3. Similar results were obtained with the solubilized preparation which was pretreated with guanylyl-5'-imidodiphosphate before solubilization. On the other hand, the effect of pentobarbital was not modified by the treatment of the synaptic membrane with pertussis toxin. These findings indicate that barbiturates suppress primarily the activation of the catalytic unit through the coupling with guanine nucleotide-binding stimulatory protein (Ns) without affecting the inhibitory protein (Ni).