Cyclic 3', 5'-AMP relay in dictyostelium discoideum. IV. Recovery of the cAMP signaling response after adaptation to cAMP

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Abstract
In D. discoideum an increase in extracellular cAMP activates adenylate cyclase leading to an increase in intracellular cAMP and the rate of cAMP secretion. Cells adapt to any constant cAMP stimulus after several minutes but still respond to an increase in the concentration of the stimulus. The decay of adaptation (deadaptation) after the removal of cAMP stimuli was characterized. Levels of adaptation were established by the perfusion of [3H]adenosine-labeled amoebae with a defined cAMP stimulus. After a variable recovery period, the magnitude of the signaling response to a 2nd stimulus was measured; its attenuation was taken as a measure of residual adaptation to the 1st stimulus. The level of adaptation established by the 1st stimulus depended on its magnitude and duration. Deadaptation began as soon as the 1st stimulus was removed. The magnitude of the response to the 2nd stimulus increased with the recovery time in a 1st-order fashion, with a t1/2 = 3-4 min for stimuli of 10-8 M to 10-5 M cAMP. Responses to test stimuli, had an accelerated time-course when they closely followed a prior response that had not completely subsided. This effect is called priming; we believe it reveals a reversible, rate-limiting step that modulates the onset and termination of the signaling responses of amoebae that have not recently responded to a cAMP stimulus. The cAMP signaling response may be controlled by 2 antagonistic cellular processes, excitation and adaptation. The data reported here implies that both the rate of rise in the adaptation process and the final level reached depend on the occupancy of cAMP surface receptors and that the decay of adaptation when external cAMP is removed proceeds with 1st-order kinetics.