My understanding of receptor downregulation is that when activated, a receptor then gets absorbed into its cell, as shown in this weird video. It then gets either recycled or degraded. Tolerance presents when more degradation than usual happens.
- Receptor activated (ligand binds to receptor)
- Receptor-ligand complex internalized to cell
- Some complexes recycled, others degraded
- Tolerance = more degradation than usual, resulting in lower receptor density at cell surface (called downregulation)
So, what is causing the higher degradation than usual? Is it the lack of the materials required to produce the receptor? If so, can this be compensated for via diet or supplementation (i.e. eating more dopamine precursors if you're trying to avoid dopamine receptor downregulation, for example?)