Dopamine D2 and D3 receptors inhibit dopamine release.

D2-like dopamine receptors are thought to control presynaptic dopamine synthesis and release. Because these receptors comprise a family which includes D2, D3 and D4 dopamine receptors, the question arises as to which subtype performs what role(s). To investigate the potential autoreceptor roles of these proteins, D2, D3 and D4 receptors were transfected into a mesencephalic clonal cell line which synthesizes and releases dopamine. Here we report that stimulation of transfected D2 and D3 receptors, but not D4 receptors, inhibits dopamine release from this dopaminergic cell line. This is the first report of a functional role for D3 receptors and establishes these cell lines as a convenient in vitro model system to study signal transduction mechanisms associated with autoreceptor function.