Regulation of neurosecretory habituation by cAMP. Role of adaptation of cAMP signals.

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.