β(2)-Adrenergic receptor polymorphisms and signaling: Do variants influence the "memory" of receptor activation?

Nonsynonymous, coding sequence single-nucleotide polymorphisms in β(2)-adrenergic receptors were first recognized almost 20 years ago, but a full understanding of their impact on signal transduction-especially on receptor abundance in native cells and their clinical importance-remains unclear. New evidence has revealed a feature of the Arg(16)Gly variant of β(2)-adrenergic receptors that has not been previously noted: a difference in the rate of response upon repeated stimulation of the receptors, such that the Arg(16) variant shows slower activation and the Gly(16) variant faster activation of cyclic adenosine monophosphate (cAMP) formation-a feature that the authors term "receptor memory." This is an intriguing idea but will require confirmation and demonstration of its functional importance in vivo and its possible contribution to clinical responses, especially in terms of the administration of β(2)-adrenergic agonists.