Agonist-induced regulation of the neuronal nicotinic XXXX receptor of PC12 cells.

@entity1911 @entity6959 @entity1617 @entity5402 @entity934
@entity1911 cells, clone PC12, possess neuronal nicotinic @entity934 ( @entity1617 ) receptors which can be activated by an agonist to produce a transient transmembrane cation flux similar to that seen with neuromuscular nicotinic ACh receptors. We have observed that these neuronal nicotinic ACh receptors are subject to long term regulation by the cholinergic agonist @entity5402 ( @entity5402 ). Receptor function was measured by agonist-induced uptake of 86Rb+ into the cells. Chronic exposure to concentrations of @entity5402 that caused receptor activation induced an adaptation (down-regulation) of the receptors, seen as a decrease in the responsiveness of the cells to a subsequent exposure to @entity5402 . The extent of the decreased responsiveness was proportional to the concentration of @entity5402 between 50 microM and 10 mM and was distinct from acute receptor desensitization. The concentrations of @entity5402 that caused down-regulation were greater than those that caused maximum receptor activation, but were similar to those that greatly enhanced desensitization. This suggested that promotion of the desensitized state of the receptor could be the true stimulus for down-regulation. Adaptation was observed initially after several hours of exposure and maximally within about 7 days. Recovery from the down-regulated state required several days of growth in the absence of @entity5402 . Treatment with the antagonist @entity6959 did not cause a similar change in the responsiveness of the cells. However, concurrent exposure to @entity5402 and @entity6959 prevented down-regulation. Therefore, it appeared that receptor activation was necessary for regulation to occur. Comparison of the cellular responses of chronically treated and control cells to acute stimulation with @entity5402 supported the hypothesis that the mechanism for this down-regulation in PC12 cells was a decrease in the number of functional ACh receptors.
