The same receptor can relay its signal through several routes. In GPCRs, the two main ones are activation of the G protein, which generates second messengers such as cyclic AMP, and recruitment of β-arrestins, which uncouple the receptor, internalise it and trigger signals of their own.
The natural hormone balances those routes in a certain way. A synthetic agonist can favour one over another. That has practical consequences: an agonist that recruits less β-arrestin may cause less receptor internalisation and therefore less loss of response with continuous exposure.
This concept has been discussed, for example, to explain part of tirzepatide's profile at the GLP-1 receptor, and it is an active area in the design of new incretin, opioid and other GPCR agonists.
Biased agonism explains why two agonists of the same receptor, with similar potencies, can behave differently in long-term studies.
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- Pharmacodynamics: receptors and signaling · Module 2
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Definition for educational and scientific purposes. It is not medical advice or a recommendation for use. NeoPeptidos products are sold labelled for research use only (RUO).