The D 1 dopamine receptor, G protein ␥ 7 subunit, and adenylylcyclase are selectively expressed in the striatum, suggesting their potential interaction in a common signaling pathway. To evaluate this possibility, a ribozyme strategy was used to suppress the expression of the G protein . Studies suggest that imbalances between these two opposing classes lead to deficiencies in movement and cognitive performance (2, 3). In particular, alterations in the D 1 -like dopamine receptors are implicated in a variety of neurologic and psychiatric disorders, such as Parkinson's disease, Tourette's syndrome, and schizophrenia. Thus, achieving a better understanding of the D 1 -like dopamine receptors and the signaling pathways they activate may suggest more selective therapeutic targets in these diseases.The D 1 and D 5 dopamine receptors stimulate adenylylcyclase activity through their coupling to heterotrimeric G proteins (1, 4 -6). Because the function of these heterotrimeric G proteins was originally ascribed to the ␣ subunit, most research has focused on determining its identity. Of the several ␣ subunits identified to date, reconstitution studies have shown that coupling of D 1 dopamine receptors to adenylylcyclase can be mediated only by the ␣ s and ␣ olf subunits of the G s subclass (4, 5, 7-9). Although sharing 88% amino acid homology, the ␣s and ␣ olf subunits show very divergent expression patterns, ranging from the ubiquitous expression of the ␣ s subunit to the olfactory and neuron-specific expression of the ␣ olf subunit (10). Immunoprecipitation studies (11) have confirmed the interaction between the ␣ s subunit and the D 1 dopamine receptors in cells, whereas in situ hybridization (12, 13) and gene targeting (14) studies have suggested a possible interaction between the ␣ olf subunit and the D 1 dopamine receptor in striatum.By contrast, little effort has focused on determining the identity of the ␥ subunits of the G protein despite mounting evidence for their importance in receptor recognition (15,16). Of particular interest, reconstitution studies (17-21) and reverse genetic approaches (22,23) have shown that the nature of the ␥ subunit is an important determinant of its interaction with receptor. Consistent with such a role, 12 ␥ subunit genes have been identified that show extensive structural diversity (24). Recently, we used a ribozyme approach to begin to elucidate their functions (23,25,26). This approach identified the ␥ 7 subunit as a specific component of the G protein that couples the -adrenergic receptor, but not the prostaglandin E 1 receptor, to stimulation of adenylylcyclase in HEK 293 cells (23). Although expressed in a variety of tissues and cell types (27,28), the ␥ 7 subunit expression is most abundant in medium spiny neurons in striatum (13). This pattern of expression is shared by the D 1 dopamine receptor and adenylylcyclase (4, 12, 29 -31), raising the possibility that all of these components may be involved in the same signaling pathway. In the present study, we used the ribozyme ...