Cyclic 3', 5'-AMP relay dictyostelium discoideum. V. Adaptation of the cAMP signaling response during cAMP stimulation

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Abstract
In D. discoideum, extracellular cAMP activates adenylate cyclase, which leads to an increase in intracellular cAMP and the rate of cAMP secretion. The signaling response to a constant cAMP stimulus is terminated after several minutes by an adaptation mechanism. The time-course of adaptation to stimuli of 10-6 or 10-7 M cAMP was assessed. A perfusion technique was used to deliver defined cAMP stimuli to [3H]adenosine-labeled amoebae and monitor their secretion of [3H]cAMP. Amoebae were preteated with 10-6 or 10-7 M cAMP for periods of 0.33-12 min and then immediately given test stimuli of 10-8 M to 2.5 .times. 10-7 M cAMP. The response to a given test stimulus was progressively attenuated and finally extinguished as the duration of the pretreatment stimulus increased. During pretreatment with 10-6 M cAMP, the rates of attenuation could be ranked according to the concentration of the test stimulus. The responses to test stimuli of 10-8, 5 .times. 10-8, 10-7 or 2.5 .times. 10-7 M cAMP were extinguished after .apprx. 1, 2.25, 2.5 and 10 min, respectively. Stimulation for 1.5 min with 10-7 M cAMP was necessary to extinguish the response of a test stimulus of 10-8 M cAMP. The data suggests that adaptation begins within 20 s of stimulation, rises rapidly for .apprx. 2.5 min and reaches a plateau after .apprx. 10 min. The absolute rate of rise was faster during pretreatment with 10-6 than with 10-7 M cAMP. These results support a working hypothesis in which the occupancy of surface cAMP receptors leads to changes in 2 opposing cellular processes, excitation and adaptation, that control the activity of D. discoideum adenylate cyclase.