Inhibition of dopamine agonist-induced phosphoinositide hydrolysis by concomitant stimulation of cyclic AMP formation in brain slices.

Inhibition of dopamine agonist-induced phosphoinositide hydrolysis by concomitant stimulation of cyclic AMP formation in brain slices.
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通过同时刺激脑切片中环磷酸腺苷的形成来抑制多巴胺激动剂诱导的磷酸肌醇水解。

DOI:
10.1046/j.1471-4159.1994.63010222.x
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发表时间:
1994
影响因子:
4.7
通讯作者:
Friedman,E
Friedman,E
中科院分区:
医学2区
文献类型:
--
作者:
Undie,AS;Friedman,E

文献摘要

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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 activatorSp‐cyclic adenosine monophosphothioate (Sp‐cAMPS) significantly inhibited inositol phosphate formation stimulated by the dopamine D1receptor agonist SKF 38393. Conversely, the protein kinase A antagonistRp‐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 D1receptor agonists SKF 38393 and fenoldopam were shifted to the left and maximal agonist responses were markedly increased. The agonist EC50values, however, were not significantly altered by protein kinase A inhibition. NeitherSp‐cAMPS norRp‐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 D1receptor‐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.