Down-regulation is an adaptation of the cell to a situation of overstimulation and subsequent too large effect in the cell.The upper part of the graphic shows 3 consecutive steps of down-regulation. This process occurs for example when an agonist is added to a normal situation

(1). The cell is overly stimulated by the agonist for a prolonged period of time

(2). By decreasing the expression of the receptor the cell protects itself against continuous stimulation

(3). The lower part shows the different mechanisms by which the down-regulation can be performed. Signal transduction from activated receptors and signals from a high rate of internalisation result in decreased gene expression and corresponding receptor synthesis. Also more receptors are degraded and less receptors are recycled back to the membrane.

An example: receptor down-regulation occurs in diabetes type II patients using insulin.