NEUROSECRETORY HABITUATION IN PC12 CELLS - MODULATION DURING PARALLELHABITUATION

PC12 cells habituate during repetitive stimulation with acetylcholine, bradykinin, or high potassium. Interspersing these stimulants did not affect the rate of habituation of the others, but it could modulate t he amplitude of the norepinephrine secretion each could achieve. Stimu lation with acetylcholine inhibited norepinephrine secretion caused by high potassium and bradykinin stimulation, while high potassium had n o effect on acetylcholine or bradykinin, and bradykinin increased secr etion caused by acetylcholine. Changes in norepinephrine secretion res ulting from any of these stimulants correlated with changes in interna l calcium levels. Cyclic AMP-, protein kinase C-, and calmodulin-depen dent second messenger path ways all modulated norepinephrine secretion caused by acetylcholine and high potassium and showed a distinct hier archy in their effectiveness. These data demonstrate that different re ceptor pathways can change the norepinephrine response of one another while not changing the levels of the molecules responsible for habitua tion.