Dopamine receptor stimulation decreases cytosolic gamma protein kinase C immunoreactivity in rat hippocampal slices: evidence for increased Ca(2+)-dependent proteolysis.

Abstract

The effect of dopamine (DA) receptor stimulation on the distribution of gamma protein kinase C (gamma PKC) in hippocampal slices was assessed. Nanomolar concentrations of DA decreased cytosolic gamma PKC (56%) without altering membrane gamma PKC levels, resulting in decreased total gamma PKC immunoreactivity. The maximal decrease in cytosolic gamma PKC occurred at 20 min of incubation and was significantly blocked by the D1 DA antagonist SCH 23390 (10(-6) M) but not by the D2 antagonist sulpiride (10(-5) M). The D1 agonists SKF 38393 and A 77636 mimicked the effect of DA with similar responses produced at 10 microM and 1 nM, respectively. The D2 agonist quinpirole had no effect on gamma PKC immunoreactivity, thus indicating that this dopaminergic response is mediated through a D1-like receptor. DA had no effect on alpha, delta, or zeta PKC isozyme immunoreactivity in the same hippocampal preparations. The DA-induced decrease in cytosolic gamma PKC immunoreactivity was blocked by the Ca(2+)-dependent protease inhibitor N-acetyl-Leu-Leu-norleucinal (100 microM) and by the inorganic Ca2+ channel blocker Co2+. The data suggest that DA stimulates a D1-like DA receptor, which increases the influx of Ca2+ and activates the Ca(2+)-dependent proteolysis of gamma PKC.