Interferon-Mediated Inhibition of Adenylate Cyclase in Mouse Cells

Abstract

Adenylate cyclase activity was measured in mouse cell plasma membrane after 30 units/ml of interferon (IFN) treatment. The basal and G_PP(NH)_P* stimulated enzyme activity in L_B cell was inhibited by 20%–40% throughout the time course of treatment (30 min to 18 h). The reduced enzyme activity was not associated with enhanced breakdown of cAMP, but was related to alteration in the catalytic component of the enzyme. Moreover, there was no change in the affinity for guanine–nucleotide regulatory unit and 1 × 10⁻⁷ M G_PP(NH)_P was required to obtain half-maximal activation with either type of membrane. Interferon action on adenylate cyclase was biphasic, at 10 u/ml it was stimulatory and between 30 and 1000 u/ml it inhibited the enzyme activity to a great extent; but IFN did not exert its effect directly on the enzyme. The reduction in enzyme activity was comparable to a reduction in the intracellular level of cAMP in most of the interferon-sensitive cell lines studied. We propose, therefore, that the inhibitory effect on adenylate cyclase is related to a step in the development of antiviral activity.