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, as well as the identity of cells expressing it, are still poorly defined. Using quantitative polymerase chain reaction we detected the messenger RNA of the D-4, but not other D-2-like receptor, in cultured granule cells from neonatal rat cerebellum. In these neurons, dopamine reduced high-voltage-activated calcium current, with a pharmacology corresponding 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 present and D-4 receptor messenger RNA had declined. The dopamine response 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 isobutylmethylxanthine. These results indicate the presence in the neonatal cerebellum of a functional D-4 receptor inhibiting an L-type calcium current, an action involving a Gi/Go protein but independent from adenylate cyclase inhibition.