The role of adaptation in receptors was studied with regard to the processing of neural information by cAMP in PC12 cells. Both secretin and adenosine A2 receptors elevated cAMP levels. During prolonged stimulation, secretin receptors demonstrated adaptation of cAMP levels, while adenosine A2 receptors did not. Incubation of cells with secretin increased the norepinephrine secretion resulting from stimulation by acetylcholine, but not from high potassium depolarization. The difference in the adaptation of cAMP by secretin and adenosine A2 receptors was responsible for the changes observed in norepinephrine secretion. This difference in secretory responses was caused by protein-kinase-C activation, which occurred during acetylcholine stimulation but not during depolarization by high potassium. Secretin receptors also demonstrated a reduced ability to elevate cAMP levels during repetitive stimulation, even for stimulation times where no adaptation of cAMP signals was observed, suggesting that secretin receptors possess the ability to habituate in addition to undergoing adaptation. These results are discussed with regard to the modulatory roles cAMP may play in neurosecretory habituation.Habituation of norepinephrine secretion in PC12 cells in response to repetitive stimulation serves as a model for understanding simple memory processes at the molecular level. Habituation is a process of learning in which an organism diminishes its responsiveness during repetitive stimulation [l]. PC12 cells demonstrate habituation as measured by norepinephrine secretion in response to repetitive depolarization or repetitive acetylcholine stimulation 12-41. The extent of habituation depends on the strength and frequency of the stimulus, and the cells can recover their secretory responsiveness when sufficient rest time exists between stimulations [2-41. Repetitive dcpolarization of PC12 cells with high POtassium causes a rcduction in the intracellular calcium elevation achieved during successive stimulations and, in this case, the reduction in calcium levels accounts for over 90% of measured habituation in norepinephrine secretion [5].In this paper, we address not only habituation but the role of adaptation of receptors. As these tcrms are often used by neuroscientists and biochemists in different ways, it is important to explain what exactly we mean by each of these terms. In this paper, we shall use the term habituation to refer to the diminution of a response to a repetitive stimulation. An example is shown in Fig. 1A. Here, a stimulus is delivered for a set time at defined intervals, leading to a reduced response during each subsequent stimulation. By definition, increasing the interstimulus interval eventually should lead to a situation in which no habituation is observed. We shall define adaptation as the diminution of a response during a single stimulation when it is applied at constant strength (Fig. 1B). If the response returns to the level seen prior to stimulation, it is termed complete adaptation. If the response does no...