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Published on: February 18, 2014
Biased Signaling as Allosteric Probe Dependence: Everything Old Is New Again
1Department of Pharmacology, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 27599, United States.
None:
This chapter considers biased signaling as a natural function of GPCRs in the form of probe dependence. Thus, any ligand that changes the conformation of the receptor (agonist, antagonist, allosteric modulator) has the potential to change the natural signaling of the receptor through diverse conformational alterations in the receptor structure. Given this, selectivity is discussed in terms of varying intrinsic efficacy and selective stabilization of receptor states with methods to detect and measure these effects. Lastly, the translation of in vitro to complex in vivo systems will be considered.
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