Signal transduction via G-protein coupled receptors (GPCRs) relies upon the production
of cAMP and other signaling cascades. A given receptor and agonist pair, produce
multiple effects upon cellular physiology which can be opposite in different cell types.
The production of variable cellular effects via the signaling of the same GPCR in different
cell types is a result of signal organization in space and time (compartmentation).
This organization is usually based upon the physical and chemical properties of the
membranes in which the GPCRs reside and the repertoire of downstream effectors and
co-factors that are available at that location. In this review we explore mechanisms of
GPCR signal compartmentation and broadly review the state-of-the-art methodologies
which can be utilized to study them. We provide a clear rationale for a “localized”
approach to the study of the pharmacology and physiology of GPCRs and particularly
the secondary messenger cAMP.