Research ArticleGPCR SIGNALING

A Polymorphism-Specific “Memory” Mechanism in the β2-Adrenergic Receptor

Science Signaling  09 Aug 2011:
Vol. 4, Issue 185, pp. ra53
DOI: 10.1126/scisignal.2001681

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Receptor Memory

Drugs that activate the β2-adrenergic receptor (β2AR), or β2AR agonists, are used to treat various conditions, such as asthma and premature labor contractions. Frequently occurring polymorphisms that result in amino acid substitutions at position 16 in the β2AR have been correlated to different responses to these drugs. Ahles et al. (see also the Perspective by Insel) found that the β2AR responded differently to repeated drug stimulation, a phenomenon the authors call receptor “memory.” A variant of the β2AR with arginine at position 16 was slower in response to repeated stimulation. In contrast, a polymorphic variant of β2AR with glycine at position 16 showed faster activation when repeatedly stimulated, an effect that was associated with increased production of a downstream signaling molecule. The authors propose that these polymorphism-specific responses of the β2AR to continued stimulation may contribute to individual variation in responses to β2AR agonists.