Dopamine decreases striatal enkephalin turnover and proenkephalin messenger RNA abundance via D2 receptor activation in primary striatal cell cultures

C Kowalski, P Giraud - Neuroscience, 1993 - Elsevier
C Kowalski, P Giraud
Neuroscience, 1993Elsevier
Dopaminergic regulation of striatal enkephalin biosynthesis and secretion was studied in
primary neuronal cultures from fetal rat striatum. To allow pharmacological treatment, striatal
primary cell cultures were seeded in chemically defined medium onto extracellular matrix. In
these conditions, pharmacological treatment of the striatal neurons on the 10th day in vitro
for 48 h with 10− 6 M dopamine induced a 50% decrease in preproenkephalin mRNA level
concomitant with a 50% decrease in methionine enkephalin neuronal content. These effects …
Abstract
Dopaminergic regulation of striatal enkephalin biosynthesis and secretion was studied in primary neuronal cultures from fetal rat striatum. To allow pharmacological treatment, striatal primary cell cultures were seeded in chemically defined medium onto extracellular matrix. In these conditions, pharmacological treatment of the striatal neurons on the 10th day in vitro for 48 h with 10−6 M dopamine induced a 50% decrease in preproenkephalin mRNA level concomitant with a 50% decrease in methionine enkephalin neuronal content. These effects of dopamine were mimicked by the D2 agonist bromocriptine (10−6M). The decrease in methionine enkephalin neuronal content induced by dopamine or bromocriptine was reversed by the simultaneous application of sulpiride (10−6M), a selective D2 antagonist. Interestingly, the D1 agonist SKF 38393 (10−6 M) application for 24 or 48 h was found to have no significant effect on methionine enkephalin neuronal content. To ensure dopamine regulation of enkephalin secretion, shorter dopaminergic treatments were performed. Dopamine application (10−6M) for 2 h had no significant effect on basal methionine enkephalin secretion but significantly decreased (50%) methionine enkephalin secretion induced by KC1 56 mM. This effect of dopamine on the KCl-induced methionine enkephalin secretion was mimicked by bromocriptine (10−6M), reversed by sulpiride (10−6M) and unaffected by the D1 antagonist SCH 23390 (10−6M) application onto striatal neurons.
Our data provide direct evidence for a dopaminergic inhibitory control on enkephalin biosynthesis and secretion from striatal cell cultures, mediated through the dopaminergic D2 receptor activation.
Elsevier