GOLFa Mediates Dopamine D1 Receptor Signaling

It is generally assumed that the coupling of dopamine D1 receptors to adenylyl cyclase is mediated by the stimulatory GTP-binding protein Gs. However, the striatum contains little Gsa subunit, whereas it expresses high levels of Golfa, a close relative of Gsa that is also expressed in olfactory receptor neurons. We used Golfa knockout mice to examine the functional coupling of D1 receptors. We found that these mice showed no hyperlocomotor response to either the D1 agonist SKF-81297 or the psychostimulant cocaine. Moreover, Golfa knockout mice did not display cocaine-induced c-fos expression in the striatum. Finally, in the absence of Golfa, striatal D1 receptors have a decreased affinity for dopamine. Thus coupling to Golfa appears to mediate D1 signaling in the striatum.