Regulation of muscarinic cholinergic receptor density in neuroblastoma cells by brief exposure to agonist: Possible involvement in desensitization of receptor function

Cell membrane surface muscarinic receptors on mouse neuroblastoma cells (clone N1E-115) are subject to a rapid receptor-mediated regulation upon contact with receptor agonists. Pre-treatment of cells for 30 min at 37°C resulted in a significant reduction in the specific binding of the hydrophilic ligand N-[³H] methylscopolamine. The magnitude of the reduction was dependent on agonist concentration and temperature. The phenomenon also demonstrated saturability. Further characterization of this reduced binding revealed that it is a 'true' disappearance of the cell membrane surface receptors and that receptor activation is needed to trigger this receptor regulation. Once the agonist was removed, almost complete recovery of the cell membrane surface receptors was seen within 30 min at 37°C. A number of similarities have been demonstrated to exist between agonist-induced desensitization of receptor-mediated increase in cyclic GMP formation and agonist-induced receptor regulation, which suggests that both phenomena might be related.