Receptor recycling is a necessary process to end signalling and allow deactivated receptors to be reinserted into the membrane.
Activated receptors are removed from the membrane by endocytosis, bringing the entire receptor into the cytoplasm in an endosome. Enzymes are then used to detach or degrade the ligand, before the receptor, in its inactive form, is reinserted into the membrane. This process is used with G-protein coupled receptors (GPCRs), allowing signalling to be terminated if the ligand does not dissociate endogenously.
The rate of receptor recycling may need to be determined, especially if it impacts on the drug’s half-life and biological activity. This could make targeting certain receptors more challenging, especially if the recycling rate is very high.
Receptor recycling does not impact allosteric modulation differently to orthosteric antagonists. As the entire receptor is intracellularised, the binding site of the ligand is not an impacting factor.