Fig. 1.

Schematic representation of the ligand-binding between epinephrine (red dots on the top-left) and GPCRs (left, formed by seven cylindrical Transmembrane Domains-TMs) with production of intracellular and extracellular cyclic-Adenosine MonoPhosphate-cAMP- in the presence of transporters-MRPs (yellow unit to the right). Intermediate units are the G-protein (brown circle, near the GPCRS) and the Adenylate Cyclase (purple unit, across the membrane). The surface density of GPCRs bound to ligands is denoted by ξ, while the analog for MRPs is labelled as ζ. The letters A, B, C and D display the order in which the chain of events occurs from the time in which ligand-binding takes place to the effects of the cell response through the production of intracellular and extracellular cAMP. The scheme highlights that a broad spectrum inhibitor of cAMP phosphodiesterase, labelled as PDE, is accounted for (Biondi et al., 2010). Helical domains forming the GPCR are displayed as cylinders in the figure: the TMs, where TM3, TM5 and TM6 have been reported in colors, to highlight their conformational changes.   The latter are displayed at the bottom of this figure. They consist in a rotation (ω) of such domains about their axis, orthogonal to the (local) mid plane of the membrane (whose unit vector is denoted by e₃), and on the shear (μ) of TM6 approximately towards TM5, in the direction s, whose components in the local mid-plane are also displayed in the figure (see e.g. Ghanouni et al., 2001). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)