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(-6) M DA. The peak response was observed at 2-3 min after addition of 10(-4) M DA, but [3H]PdBu binding was still increased above basal at 30 min. DA was not acting via an adrenergic receptor. Prazosin (10(-6) M) blocked the response to NE, suggesting mediation by an alpha 1-adrenergic receptor, but had little effect on the response to DA. Conversely, the D1 receptor antagonist SCH-23390 (10(-6) M) blocked the response to DA, but only partially inhibited the response to NE. Morphine (10(-6) M) 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.

Dopamine D1A Receptor Regulation of Phospholipase C Isoform

“…Although the present finding indicates that PLC stimulation in these transfected cells is secondary to adenylyl cyclase stimulation, several studies in tissues have implicated the existence of a D 1 -like receptor that is linked to phospholipase activation independent of adenylyl cyclase (9,11,13,14). Activation of D 1 -like receptors decreases sodium transport by cAMP-dependent (42)(43)(44) and cAMP-independent mechanisms (45)(46)(47)(48).…”

Dopaminergic regulation of transcription factor expression in organotypic cultures of developing striatum

“…Stimulation of Dl-like receptors has been shown to activate protein kinase C in striatal cell cultures (McMillian et al, 1992), and activated protein kinase C can induce c-fos in transfected cell lines (Fisch et al, 1987;Gilman, 1988). We were unable to demonstrate convincingly that activation of protein kinase C with PMA induced expression of Fos-like protein in the cultured striatum.…”

Developing a Neuronal Model for the Pathophysiology of Schizophrenia Based on the Nature of Electrophysiological Actions of Dopamine in the Prefrontal Cortex

“…These changes in I NaP kinetics by PKC activation are remarkably similar to that following dopamine or D1/5 agonist application in PFC neurons as mentioned above (Gorelova and Yang, submitted; Gorelova and Yang 1997b). There is some evidence for activation of PKC by dopamine and D1 agonists (McMillian et al 1992;Kansra et al 1995). This finding raises the question of whether dopamine may modulate I NaP in PFC neurons via activation of PKC; whereas, dopamine induces changes in fast Na ϩ current in striatal neurons via activation of PKA.…”