Trends in Pharmacological Sciences
Differences between natural and recombinant G protein-coupled receptor systems with varying receptor/G protein stoichiometry
Section snippets
High-affinity selection
It is well known that agonists can demonstrate high affinity for receptor states due to the promotion of G protein coupling. In many natural receptor systems, the amount of G protein available for formation of such complexes is not limiting, and the complete receptor population can be converted into a high affinity ternary complex by an efficacious agonist. However, in some systems, the availability of G protein is limiting. This leads to differences in the amount of total receptor density when
Functional receptor studies
Further complexities can arise when there is more than one receptor-derived species producing the measured signal. Binding usually yields a relative quantity of receptor (albeit in various states of complexation and/or conformation), and functional studies yield a product of receptor state(s) which then go on to interact with other membrane and cytosolic components. Possible differences between natural and recombinant receptor systems arise, if the recombinant system possesses any constitutive
Concluding remarks
In general, the lack of adherence to criteria defining simple binding for receptors augurs non-equilibrium steady states and not differences in the nature of drug and drug–receptor interaction. However, in recombinant receptor systems with altered stoichiometry between receptors and G proteins, extreme differences can cause displacement curves that apparently adhere to Langmuirian kinetics and therefore could be interpreted erroneously. Alternatively, such differences can bestow apparent
Acknowledgements
Acknowledgement
I wish to thank Mrs McGhee for her expert assistance in the preparation of this manuscript.
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