Specificity of Muscarinic Acetylcholine Receptor Regulation by Receptor Activity |
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Authors: | Robert G Siman William L Klein |
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Institution: | Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60201, U.S.A. |
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Abstract: | Abstract— Regulation of muscarinic acetylcholine receptor concentration by receptor activity in neuron-like NG108-15 hybrid cells is a highly specific process. Receptor levels, monitored by binding of 3H]quinuclidinyl benzilate (3H]QNB), decreased 50-75% following 24-h incubation of cells with muscarinic agonists, but none of the following cellular processes was altered by this chronic receptor stimulation: (1) glycolytic energy metabolism, measured by 3H]deoxy- d -glucose (3H]DG) uptake and retention; (2) rate of cell division; (3) transport, measured by 3H]valine and 3H]uridine uptake; (4) RNA biosynthesis, measured by 3H]uridine incorporation; (5) protein biosynthesis, measured by 3H]valine and 35S]methionine incorporation into total protein and into protein fractions obtained by polyacrylamide gel electrophoresis. In contrast, chronic stimulation did cause a threefold decrease in the capacity of carbachol to stimulate phosphatidylinositol (PI) turnover, a receptor-mediated response. In addition to cholinomimetics, the neuroeffector adenosine (1 m m for 24 h) also caused a decrease in 3H]QNB binding levels, but chronic stimulation of α -adrenergic, opiate, prostaglandin E1, and prostaglandin F2α receptors found on NG108-15 cells caused no changes. The data indicate that loss of muscarinic receptors caused by receptor stimulation is not a consequence of fundamental changes evoked in overall cellular physiology but reflects a specific regulation of cholinoceptive cell responsiveness. |
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Keywords: | Synaptic plasticity Neuron 2 Deoxy d glucose Phosphatidylinositol Cell culture |
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