A single G-protein-coupled receptor might activate multiple G-protein speci
es. This multiplex coupling ability can be used by tissues to regulate sign
alling; for the pharmacologist, such multiplex coupling might cause difficu
lties in the interpretation of experimental data. In this article, we prese
nt mathematical models for the activation of two separate G-protein species
by a single receptor. Issues addressed concern mutual antagonism between t
he G proteins and the availability of an already activated receptor for int
eraction with a new G protein (receptor-G-protein-effector complexing versu
s free diffusion of G proteins) in addition to receptor-G-protein precoupli
ng at different G-protein and receptor expression levels. The output from t
he receptor models uses, as readout, a new model for adenylyl cyclase regul
ation by two allosteric regulators (i.e. G(s) and G(i)).