Adenosine receptors and membrane microdomains

Adenosine receptors are a member of the large family of seven transmembrane spanning G protein coupled receptors. The four adenosine receptor subtypes—A1, A2a, A2b, A3—exert their effects via the activation of one or more heterotrimeric G proteins resulting in the modulation of intracellular signaling. Numerous studies over the past decade have documented the complexity of G protein coupled receptor signaling at the level of protein–protein interactions as well as through signaling cross talk. With respect to adenosine receptors, the activation of one receptor subtype can have profound direct effects in one cell type but little or no effect in other cells. There is significant evidence that the compartmentation of subcellular signaling plays a physiological role in the fidelity of G protein coupled receptor signaling. This compartmentation is evident at the level of the plasma membrane in the form of membrane microdomains such as caveolae and lipid rafts. This review will summarize and critically assess our current understanding of the role of membrane microdomains in regulating adenosine receptor signaling. This article is part of a Special Issue entitled: “Adenosine Receptors”.

Research Highlights
► A1 adenosine receptors in cardiomyocytes are localized in caveolae.
► A1 adenosine receptors in other cell types appear to internalize via caveolae.
► A2a adenosine receptors may be concentrated in cholesterol enriched membrane domains.
► There is no evidence to date for localization of A2b or A3 receptors in membrane microdomains.