Abstract
Effects of dopaminergic drugs on the degranulation of mast cells (RBL-2H3 cells) and the nitric oxide production from macrophage cells (RAW 264.7) were studied. Among the dopaminergic agonists and antagonists tested, bromocriptine, 7-OH-DPAT, haloperidol, and clozapine showed potent inhibitions of mast cell degranualtion (IC50 value, 5 microM). However, these dopaminergic agents did not affect the tyrosine phosphorylations of the signaling components of the high affinity IgE receptor (FcepsilonRI), such as Syk, PLCgamma1, and PLCgamma2.; This suggested that these signaling components were not involved in the inhibition of the mast cell degranulation by these compounds. On the other hand, dopamine, bromocriptine, 7-OH-DAPT, and haloperidol markedly inhibited the nitric oxide production from RAW 264.7 cells (IC50 values, 10-20 microM). Bromocriptine, a dopamine agonist that is routinely used for the treatment of Parkinsons disease, inhibited the expression of the inducible nitric oxide synthase at an early stage of the LPS-induced protein expression in a dose-dependent manner. The results suggested that these dopaminergic agents, when used for the treatment of dopamine receptors-related diseases, such as Schizophrenia or Parkinsons disease, might have additional beneficial effects.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bromocriptine / pharmacology
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Cell Degranulation / drug effects
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Cell Degranulation / physiology
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Cell Line, Tumor*
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Clozapine / pharmacology
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Dopamine / pharmacology
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Dopamine Agents / pharmacology*
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical / methods
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Enzyme Precursors / metabolism
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Enzyme Precursors / pharmacology
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Haloperidol / pharmacology
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Intracellular Signaling Peptides and Proteins
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Lipopolysaccharides / pharmacology
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Mast Cells / cytology*
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Mast Cells / physiology
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Mice
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Nitric Oxide / antagonists & inhibitors
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Nitric Oxide / biosynthesis*
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / biosynthesis
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase Type II
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Nitrites / metabolism
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Phospholipase C gamma
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Protein-Tyrosine Kinases / metabolism
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Protein-Tyrosine Kinases / pharmacology
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Quercetin / pharmacology
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Receptors, IgE / drug effects
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Signal Transduction / physiology
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Syk Kinase
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Tetrahydronaphthalenes / pharmacology
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Type C Phospholipases / metabolism
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Type C Phospholipases / pharmacology
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beta-N-Acetylhexosaminidases / antagonists & inhibitors
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beta-N-Acetylhexosaminidases / metabolism
Substances
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Dopamine Agents
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Enzyme Precursors
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Intracellular Signaling Peptides and Proteins
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Lipopolysaccharides
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Nitrites
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Receptors, IgE
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Tetrahydronaphthalenes
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Nitric Oxide
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Bromocriptine
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Quercetin
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, mouse
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Type C Phospholipases
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Phospholipase C gamma
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beta-N-Acetylhexosaminidases
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Clozapine
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Haloperidol
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7-hydroxy-2-N,N-dipropylaminotetralin
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Dopamine