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Inhibition of Dopamine Agonist‐Induced Phosphoinositide Hydrolysis by Concomitant Stimulation of Cyclic AMP Formation in Brain Slices
Author(s) -
Undie Ashiwel S.,
Friedman Eitan
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.1471-4159.1994.63010222.x
Subject(s) - agonist , medicine , inositol phosphate , endocrinology , chemistry , dopaminergic , adenosine , dopamine , forskolin , dopamine receptor d1 , stimulation , dopamine receptor , dopamine receptor d2 , dopamine agonist , cyclic adenosine monophosphate , receptor , biology , inositol , biochemistry
We examined the effects of cyclic AMP on dopamine receptor‐coupled activation of phosphoinositide hydrolysis in rat striatal slices. Forskolin, dibutyryl cyclic AMP, and the protein kinase A activator Sp ‐cyclic adenosine monophosphothioate ( Sp ‐cAMPS) significantly inhibited inositol phosphate formation stimulated by the dopamine D 1 receptor agonist SKF 38393. Conversely, the protein kinase A antagonist Rp ‐cyclic adenosine monophosphothioate ( Rp ‐cAMPS) dose‐dependently potentiated the SKF 38393 effect. In the presence of 200 µ M Rp ‐cAMPS, the dose‐response curves of the dopamine D 1 receptor agonists SKF 38393 and fenoldopam were shifted to the left and maximal agonist responses were markedly increased. The agonist EC 50 values, however, were not significantly altered by protein kinase A inhibition. Neither Sp ‐cAMPS nor Rp ‐cAMPS significantly affected basal inositol phosphate accumulation. These findings demonstrate that dopaminergic stimulation of phosphoinositide hydrolysis is inhibited by elevations in intracellular cyclic AMP. Dopamine receptor agonists that stimulate adenylyl cyclase could suppress their activation of phosphoinositide hydrolysis by concomitantly stimulating the formation of cyclic AMP in striatal tissue. The interaction between dopamine D 1 receptor‐stimulated elevations in cyclic AMP and dopaminergic stimulation of inositol phosphate formation suggests a cellular colocalization of these dopamine‐coupled transduction pathways in at least some cells of the rat striatum.