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Dopamine Receptor Stimulation Decreases Cytosolic γ Protein Kinase C Immunoreactivity in Rat Hippocampal Slices: Evidence for Increased Ca 2+ ‐Dependent Proteolysis
Author(s) -
YurkoMauro Karin A.,
Friedman Eitan
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65041622.x
Subject(s) - protein kinase c , medicine , endocrinology , sch 23390 , stimulation , agonist , quinpirole , biology , chemistry , dopamine receptor d2 , receptor , dopamine , kinase , biochemistry
The effect of dopamine (DA) receptor stimulation on the distribution of γ protein kinase C (γPKC) in hippocampal slices was assessed. Nanomolar concentrations of DA decreased cytosolic γPKC (56%) without altering membrane γPKC levels, resulting in decreased total γPKC immunoreactivity. The maximal decrease in cytosolic γPKC occurred at 20 min of incubation and was significantly blocked by the D 1 DA antagonist SCH 23390 (10 −6 M ) but not by the D 2 antagonist sulpiride (10 −5 M ). The D 1 agonists SKF 38393 and A 77636 mimicked the effect of DA with similar responses produced at 10 µ M and 1 n M , respectively. The D 2 agonist quinpirole had no effect on γPKC immunoreactivity, thus indicating that this dopaminergic response is mediated through a D 1 ‐like receptor. DA had no effect on α, δ, or ζPKC isozyme immunoreactivity in the same hippocampal preparations. The DA‐induced decrease in cytosolic γPKC immunoreactivity was blocked by the Ca 2+ ‐dependent protease inhibitor N ‐acetyl‐Leu‐Leu‐norleucinal (100 µ M ) and by the inorganic Ca 2+ channel blocker Co 2+ . The data suggest that DA stimulates a D 1 ‐like DA receptor, which increases the influx of Ca 2+ and activates the Ca 2+ ‐dependent proteolysis of γPKC.