G-protein coupled receptors (GPCRs) transmit their signals either through stimulatory (Gas) or inhibitory (Gai) pathways. As GPCRs often form homo- or hetero-oligomers, we studied the signal pathways in hetero-oligomers, using co- expression of Gas- and Gai-coupled serotonin receptor subtypes 5-HT1a and 5-HT7. We found that the Gai pathway was dominant in N1E cells expressing hetero-oligomers, although the agonist and antagonist binding- site of both receptor subunits were still functioning. A strong interaction between receptors subunits became obvious, because the Gai-pathway was activated even when specific stimulation of the Gas-coupled receptor subtype was stimulated. We also observed that specific blockade of the Gas-coupled receptor subtype also inhibits the Gai-pathway. Treatment with pertussis toxin, a known inhibitor of Gai, resulted in a total block of the signal pathway.