Journal article
Inhibition of Dopamine Agonist‐Induced Phosphoinositide Hydrolysis by Concomitant Stimulation of Cyclic AMP Formation in Brain Slices
Journal of neurochemistry, v 63(1), pp 222-230
Jul 1994
PMID: 7911510
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Abstract
: 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 D1 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 µMRp‐cAMPS, the dose‐response curves of the dopamine D1 receptor agonists SKF 38393 and fenoldopam were shifted to the left and maximal agonist responses were markedly increased. The agonist EC50 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 D1 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.
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Details
- Title
- Inhibition of Dopamine Agonist‐Induced Phosphoinositide Hydrolysis by Concomitant Stimulation of Cyclic AMP Formation in Brain Slices
- Creators
- Ashiwel S. Undie - Departments of Pharmacology and Psychiatry, Medical College of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.Eitan Friedman - Departments of Pharmacology and Psychiatry, Medical College of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
- Publication Details
- Journal of neurochemistry, v 63(1), pp 222-230
- Publisher
- Blackwell Science Ltd
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:A1994NT49700027
- Scopus ID
- 2-s2.0-0028357786
- Other Identifier
- 991019184045004721
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- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences