Dopamine Stimulates [³H]Phorbol 12,13‐Dibutyrate Binding in Cultured Striatal Cells

Abstract: The effect of dopamine (DA) on the binding of [³H]phorbol 12,13‐dibutyrate ([³H]PdBu) in cultured rat striatal cells was examined. DA maximally increased specific [³H]PdBu binding by 70 ± 10%, an increase comparable to that observed with norepinephrine (NE). This finding suggests that DA activates protein kinase C in cultured striatal cells, because increases in [³H]PdBu binding reflect translocation of protein kinase C. Half‐maximal stimulation was observed with 10^–6M DA. The peak response was observed at 2–3 min after addition of 10^–4M DA, but [³H]PdBu binding was still increased above basal at 30 min. DA was not acting via an adrenergic receptor. Prazosin (10^–6M) blocked the response to NE, suggesting mediation by an α₁‐adrenergic receptor, but had little effect on the response to DA. Conversely, the D₁ receptor antagonist SCH‐23390 (10^–6M) blocked the response to DA, but only partially inhibited the response to NE. Morphine (10^–6M) inhibited the response to DA by 46 ± 14%, but did not affect significantly the response to NE. The DA effect on [³H]PdBu binding is apparently independent of the increase in cyclic AMP seen on D₁ receptor activation. Forskolin, apomorphine, and the D₁ agonist SKF‐38393 all increased cyclic AMP in striatal cells, but were less effective than DA in stimulating [³H]PdBu binding. The D₂ agonist quinpirole was ineffective in stimulating either cyclic AMP or [³H]PdBu binding.