Rapid increase in guanosine 3′,5′-cyclic-monophosphate in interferon-treated mouse leukemia L1210 cells: Relationship to the development of the antiviral state and inhibition of cell multiplication

Abstract

Treatment of mouse leukemia L1210 cells with electrophoretically pure mouse interferon caused a rapid (1 to 5 min) and transitory (duration 5 to 10 min) increase in the intracellular concentration of guanosine 3′,5′-cyclic monophosphate (cyclic GMP). No significant increase in the intracellular concentration of adenosine 3′,5′-cyclic monophosphate (cyclic AMP) was observed until 2 to 3 hr after the addition of interferon. Electrophoretically pure mouse interferon caused a dose-dependent increase in the intracellular concentration of cyclic GMP at concentrations ranging from 1.0 to 10 4 unite/ml. The interferon-induced increase in cyclic GMP was abrogated by specific antibody to mouse interferon. Furthermore, interferon had no effect on the intracellular concentration of cyclic GMP in a line of L1210 cells resistant to the action of interferon. The interferon-induced increase in cyclic GMP was calcium dependent and was inhibited by indomethacin and aspirin at concentrations of 10 −7 to 10 −6 M. Depletion of intracellular calcium prior to the addition of interferon abrogated the interferon-induced increase in cyclic GMP without preventing either the development of the antiviral state or the inhibition of cell multiplication in interferon-treated L1210 cells. These results suggest that cyclic GMP may not mediate these two biologic effects of interferon but may rather reflect rapid changes in interferon-treated cells.