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 mM for 24 h) also caused a decrease in [3H]QNB binding levels, but chronic stimulation of alpha-adrenergic, opiate, prostaglandin E1, and prostaglandin F2 alpha 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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