AGONIST-INDUCED REGULATION OF THE NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR OF PC12 CELLS
- 1 January 1985
- journal article
- research article
- Vol. 27 (4), 409-417
Abstract
Pheochromocytoma cells, clone PC12, possess neuronal nicotinic acetylcholine (ACh) receptors which can be activated by an agonist to produced a transient transmembrane cation flux similar to that seen with neuromuscular nicotinic ACh receptors. These neuronal nicotinic ACh receptors are subject to long term regulation by the cholinergic agonist carbamoylcholine (carbachol). Receptor function was measured by agonist-induced uptake of 86Rb+ into the cells. Chronic exposure to concentrations of carbachol 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 carbachol. The extent of the decreased responsiveness was proportional to the concentration of carbachol between 50 .mu.M and 10 mM and was distinct from acute receptor desensitization. The concentrations of carbachol that caused down-regulation were greater than those that caused maximum receptor activation, but were similar to those that greatly enhanced desensitization. Promotion of the desensitized state of the receptor could be true stimulus for down-regulation. Adaptation was observed initially after several hours of exposure and maximally within .apprx. 7 days. Recovery from the down-regulated state required several days of growth in the absence of carbachol. Treatment with the antagonist mecamylamine did not cause a similar change in the responsiveness of the cells. Concurrent exposure to carbachol and mecamylamine prevented down-regulation. Receptor activation was necessary for regulation to occur. Comparison of the cellular responses of chronically treated and control cells to acute stimulation with carbachol supported the hypothesis that the mechanism for this down-regulation in PC12 cells was a decrease in the number of functional ACh receptors.This publication has 17 references indexed in Scilit:
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