ACTIVATION OF DOPAMINE D-4 RECEPTOR INHIBITS AN L-TYPE CALCIUM CURRENT IN CEREBELLAR GRANULE CELLS

The functions of the D-4 receptor, a newly cloned D-2-like receptor, a s well as the identity of cells expressing it, are still poorly define d. Using quantitative polymerase chain reaction we detected the messen ger RNA of the D-4, but not other D-2-like receptor, in cultured granu le cells from neonatal rat cerebellum. In these neurons, dopamine redu ced high-voltage-activated calcium current, with a pharmacology corres ponding to that of the D-4 receptor. The response declined from one to three days, when calcium currents were mostly sensitive to nifedipine , to 15 days, when nifedipine-insensitive calcium currents were also p resent and D-4 receptor messenger RNA had declined. The dopamine respo nse was abolished after pretreatment of the cells by pertussis toxin, was potentiated and made irreversible by infusion of guanosine 5'-O-(3 -thiotriphosphate) but persisted in the presence of cyclic AMP and iso butylmethylxanthine. These results indicate the presence in the neonat al cerebellum of a functional D-4 receptor inhibiting an L-type calciu m current, an action involving a Gi/Go protein but independent from ad enylate cyclase inhibition.