Effects of cholera toxin on supersensitive and subsensitive rat pineal glands: regulation of sensitivity at multiple sites.

Cholera toxin, which activates adenylate cyclase by a mechanism independent of the β-adrenergic receptor, induced more N-acetyltransferase activity in supersensitive than in subsensitive rat pineal glands. This was due to an increased response in supersensitive glands, of several of the components involved in the induction. Although there was no difference in the number of binding sites for cholera toxin, there was more toxin-stimulated adenylate cyclase activity in the supersensitive glands. There was also a larger accumulation of cyclic AMP and a greater stimulation of protein kinase activity in the supersensitive glands. It is inferred that changes in the number of β-adrenergic binding sites are not the primary basis for changes in sensitivity. Rather, there are multiple sites of regulation, possibly affected by a common mechanism.