Premium
Activation of D 1 and D 2 Dopamine Receptors Inhibits Protein Kinase C Activity in Striatal Synaptoneurosomes
Author(s) -
Giambalvo C. T.,
Wagner R. L.
Publication year - 1994
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.1471-4159.1994.63010169.x
Subject(s) - protein kinase c , chemistry , endocrinology , sch 23390 , medicine , sulpiride , apomorphine , dopamine receptor d2 , receptor , agonist , dopamine receptor , calcium , dopamine , incubation , antagonist , pharmacology , phosphorylation , biochemistry , biology
The effects of D 1 and D 2 dopamine ligands on protein kinase C (PKC) activity were examined in synaptoneurosomes. Incubation with D 1 agonists (SKF 38393, fenodopam), in the presence of calcium, decreased the soluble and increased the particulate PKC activity. These effects were reversed by SCH 23390, which by itself had the opposite effect of increasing the soluble and decreasing the particulate PKC activity. In contrast, incubation with the D 2 agonists [LY 171555, (+)‐3‐(3‐hydroxyphenyl)‐ N ‐ n ‐propylpiperidine, RU 24213] increased the soluble and decreased the particulate PKC activity. These effects were reversed by sulpiride. (−)‐3‐(3‐Hydroxyphenyl)‐ N ‐ n ‐propylpiperidine had a D 2 antagonist profile. Apomorphine showed a biphasic dose‐response change; i.e., it decreased particulate PKC activity at the D 2 receptor at low concentrations (0.1 µ M ) and increased it at the D 1 receptor at higher concentrations (10 µ M ). Pretreatment with tetrodotoxin or omission of calcium in the incubation medium did not alter the responses of the D 2 agonists, but it reversed the changes in PKC activity induced by the D 1 agonists and converted the biphasic response of apomorphine to a monophasic inhibition. These results indicate that (1) D 1 and D 2 dopamine receptors are negatively coupled to PKC and (2) the increase in particulate PKC activity seen with the D 1 drugs in the presence of calcium is mediated indirectly via a transneuronal effect.