Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of apomorphine (1-20 microM) on protein kinase activity was studied in extracts from rat peritoneal mast cells and brain tissue. Apomorphine inhibited the cyclic AMP-dependent and the calcium-plus phosphatidylserine-dependent protein kinase activity with an IC50 between 1 and 6 microM, depending on the tissue and on the protein kinase involved. This effect might explain previous results on the apomorphine-induced inhibition of histamine release in rat peritoneal mast cells.
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PMID:Inhibition of protein kinase activity by apomorphine. 301 65

Apomorphine produced biphasic changes in the activity of an endogenous, specific inhibitor of cAMP-dependent protein kinase (type I inhibitor). Small doses of apomorphine (50-100 micrograms/kg) induced an increase while high doses (1-10 mg/kg) produced a dose-dependent decrease of the type I inhibitor activity in the striatum of control rats. Prolonged treatment with nomifensin markedly reduced the response of the type I inhibitor both to low and high doses of apomorphine and shifted the dose-response curves to the right. The apomorphine-induced increase of the type I inhibitor activity in nomifensin-pretreated rats was blocked by aminophylline and by small, presynaptically active doses of haloperidol. This suggests that small doses of apomorphine stimulate presynaptic D2 receptor. The apomorphine-induced decrease of the type I inhibitor activity in nomifensin pretreated animals was enhanced by aminophylline and by presynaptically active dose of haloperidol. In contrast, this action of apomorphine was blocked by high, postsynaptically active, dose of haloperidol. It suggested postsynaptic site of action of high doses of apomorphine. Prolonged pretreatment with nomifensin resulted in subsensitivity of both presynaptic D2 and postsynaptic D1 receptors.
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PMID:The responsiveness of the endogenous inhibitor of cAMP-dependent protein kinase to apomorphine in rat striatum after prolonged treatment with nomifensin. 407 79

The effect of various doses of apomorphine on the activity of specific endogenous inhibitor of cAMP dependent protein kinase (type I inhibitor) was studied. Apomorphine produced biphasic changes in the type I inhibitor activity in rat striatum. Small doses (50-100 micrograms/kg) induced an increase while large doses (0.5-10 mg/kg) caused a dose dependent decrease of the type I inhibitor activity. The apomorphine induced increase in type I inhibitor activity was completely blocked by small, presynaptically active doses of haloperidol and chlorpromazine and by aminophylline. This suggests that small doses of apomorphine stimulate presynaptic dopamine D2-receptors. In contrast, the apomorphine induced decrease of the type I inhibitor activity was greatly potentiated by aminophylline and by presynaptically active doses of the neuroleptics, suggesting a postsynaptic site of action for large doses of apomorphine. Determination of the type I inhibitor activity is proposed as one of the biochemical tests allowing to recognize the site of action of drugs stimulating dopamine receptors.
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PMID:The effect of stimulation of pre- and postsynaptic dopamine receptors on the endogenous inhibitor of cAMP-dependent protein kinase. 609 29

Apomorphine (APO), a potent D1/D2 dopamine receptor agonist, is currently used as an antiparkinsonian drug. We have shown previously that APO stimulates synthesis and release of multiple trophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), in both mesencephalic and striatal neurons, thereby effectively preventing dopaminergic neuron loss in vitro. The present study was designed to investigate the effects of APO on fibroblast growth factor-2 (FGF-2) expression and regulation in astrocytes, and furthermore, to identify signaling mechanisms underlying these effects. Here, we show that FGF-2 expression is robustly induced in cultured astrocytes in response to APO. FGF-2 expression was proportional to APO concentration and time-dependent. Conversely, treatment with S-APO, a derivative of R-APO lacking DA receptor agonist activity, did not alter FGF-2 levels. APO treatment resulted in enhanced cytosol FGF-2 immunoreactivity, export of high MW forms of FGF-2 to the cytoplasm from the nucleus and increased extracellular release of FGF-2. Interestingly, both high and low MW forms of FGF-2 were detectable in conditioned medium of APO-treated cultures. This APO-induced effect was correlated with activation of D1 and D2 receptors, as it could be either mimicked by dopamine receptor agonists (SKF38393, quinpirole) or partially blocked by antagonists (SCH23390, SKF83566, haloperidol). Activation of the D1 receptor preferentially increased PKA activity, whereas activation of the D2 receptor only promoted phosphorylation of MAPK. Importantly, APO-modulated FGF-2 expression was independent of Akt/phosphoinositide 3-kinase signaling. These data suggest that APO can enhance biosynthesis and release of FGF-2 through activation of dopamine receptors in striatal astrocytes. Both cAMP/PKA and MEK/MAPK signaling cascades are major steps mediating this process.
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PMID:Apomorphine-induced activation of dopamine receptors modulates FGF-2 expression in astrocytic cultures and promotes survival of dopaminergic neurons. 1663 1

Apomorphine (APO), a potent D1/D2 dopamine receptor agonist, is used as an anti-parkinsonian drug. It stimulates the synthesis and release of multiple trophic factors in mesencephalic and striatal neurons, preventing the loss of dopaminergic neurons in vitro. Furthermore, APO enhances the biosynthesis and release of FGF-2 by activating dopamine receptors in striatal astrocytes, where cAMP/PKA and PKC/MAPK signalling cascades mediate this process. We investigate the effects of APO on the fibroblast growth factor-2 (FGF-2) promoter and its regulation in astrocytes and identify the transcription factor and cis element underlying these effects. In screening for cis-acting elements over the entire region of the FGF-2 promoter stimulated by APO in the astrocytes, a sequence located in the -785/-745 region was found to serve as the cis element. This element was recognized by the human myeloid zinc finger protein 1 (MZF-1) transcription factor. Introducing human MZF-1 plasmid and human MZF-1-specific siRNA has different effects on the FGF-2 promoter. Furthermore, it increases FGF-2 protein expression in HeLa cells and primary astrocytes, indicating that APO stimulates the FGF-2 promoter via the MZF-1 transcription factor. These data suggest that APO can enhance the biosynthesis and release of FGF-2 through the activation of the MZF-1 transcription factor in striatal astrocytes.
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PMID:Crucial roles of MZF-1 in the transcriptional regulation of apomorphine-induced modulation of FGF-2 expression in astrocytic cultures. 1919 27