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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.

  1. Receptor activated (ligand binds to receptor)
  2. Receptor-ligand complex internalized to cell
  3. Some complexes recycled, others degraded
  4. 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?)

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So, what is causing the higher degradation than usual? Is it the lack of the materials required to produce the receptor?

Lack of materials is almost never the reason. Receptor turnover is actively controlled by different mechanisms. Ubiquitylation is one of the common mechanisms. Ubiquitylated receptors are internalized; these internalized receptors can later on be sent back to the membrane (recycled) or be degraded depending on the conditions.

Receptor downregulation can also happen by stopping their production either at the level of transcription or translation (For an example see this).

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