Muscarinic acetylcholine receptor regulation by accelerated rate of receptor loss

Sustained activation of muscarinic acetylcholine receptors on neuron-like NG108-15 hybrid cells reduces the number of [³H]quinuclidinyl benzilate binding sites per cell as much as 88%. The response occurs at concentrations of agonists commensurate with those needed to occupy receptors and inhibit adenylate cyclase. Decreases in steady-state receptor levels persist as long as activator remains present. Withdrawal of activator results in a slow increase in receptor levels that is blocked by cycloheximide. Activation shortens receptor half-life by a factor of nearly 4, indicating that regulation occurs at the level of receptor breakdown.