The responsiveness of the endogenous inhibitor of cAMP-dependent protein kinase to isoproterenol after prolonged treatment with nifedipine.

In the present study the response of the type I inhibitor activity to isoproterenol was used as an indirect index both of cAMP generation and beta-adrenergic receptor reactivity. Our results suggest that nifedipine, after prolonged treatment, produces subsensitivity in beta-adrenergic transmission without changes in the basal level of cAMP. Administration of isoproterenol produced a dose-dependent decrease of the type I inhibitor activity (an endogenous inhibitor of cAMP-dependent protein kinase, Walsh inhibitor) in the frontal cortex and hippocampus of rats. Prolonged treatment with nifedipine (5 mg kg-1 i.p., twice daily, 21 days) did not change the basal activity of the type I inhibitor, but markedly reduced the response of the type I inhibitor activity to isoproterenol. In the treated animals a significant decrease of the type I inhibitor was seen when isoproterenol was used in much higher doses than in control rats.