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Functional selectivity (or “agonist trafficking”, “biased agonism”, “differential engagement” and “protean agonism”) is the ligand-dependent selectivity for certain signal transduction pathways in one and the same receptor. This can be present when a receptor has several possible signal transduction pathways. To which degree each pathway is activated thus depends on which ligand binds to the receptor .
Additional recommended knowledge
Functional vs. traditional selectivity
Functional selectivity has been proposed to broaden conventional definitions of pharmacology.
Traditional pharmacology posits that a ligand can be either classified as an agonist (full or partial), antagonist or more recently an inverse agonist through a specific receptor subtype, and that this characteristic will be consistent with all effector (second messenger) systems coupled to that receptor. While this dogma has been the backbone of ligand-receptor interactions for decades now, more recent data indicates that this classic definition of ligand-protein associations does not hold true for a number of compounds.
Functional selectivity posits that a ligand may inherently produce a mix of the classic characteristics through a single receptor isoform depending on the effector pathway coupled to that receptor. For instance, a ligand can not easily be classified as an agonist or antagonist, because it can be a little of both, depending on its preferred signal transduction pathways. Thus, such ligands must instead be classified on the basis of their individual effects in the cell, instead of being either an agonist or antagonist to a receptor.
It is also important to note that these observations were made in a number of different expression systems and therefore functional selectivity is not just an epiphenomenon of one particular expression system.
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|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Functional_selectivity". A list of authors is available in Wikipedia.|