Inhibition by Adenosine of Aggregation Centre Initiation and Cyclic AMP Binding in Dictyostelium

Abstract

SUMMARY: The inhibitory action of adenosine on the initiation of aggregation centre formation in starving Dictyostelium discoideum was examined and used to test assumptions of theoretical models of cyclic AMP signalling. Adenosine at 5 mm strongly inhibited aggregation centre initiation with-out preventing signal relay. Inosine or AMP at 10 mm had no effect and did not prevent the effect of adenosine. Adenosine had no effect on cellular phosphodiesterase activity, contact site A formation, or chemotaxis to small drops of cyclic AMP. The chemotactically-related responses of rapid cyclic GMP formation and changes in light scattering after pulses of cyclic AMP did not show any inhibition or decrease in sensitivity to the signal in the presence of adenosine. However, binding of 3H-labelled cyclic AMP to cell surface receptors was strongly inhibited by adenosine. The maximum inhibition was approximately 90% and was non-competitive with respect to cyclic AMP. The role of cell surface cyclic AMP receptors in the mechanism of initiation and the implications of the effects of adenosine for the role of cyclic GMP as a secondary messenger are discussed.