Abstract
Cultured murine bone marrow derived mast cells (BMMC) were found to store high levels of dopamine (3753+/-844 pg/10(7) cells) and occasionally produce norepinephrine and epinephrine. The catecholamine synthesis inhibitor, alpha-methyl-para-tyrosine, decreased intracellular catecholamine concentrations, and activation with ionomycin stimulated dopamine release. Neither dopaminergic receptor antagonists nor exogenous dopamine < or =10 microM affected IL-3-induced cell proliferation. High exogenous dopamine (20-100 microM) decreased proliferation and increased apoptosis, and the anti-oxidant ascorbic acid prevented these effects. Increased expression of the anti-apoptotic factor Bcl-2 or loss of pro-apoptotic Bax expression attenuated dopamine-induced apoptosis, suggesting the apoptosis proceeds through a mitochondrial pathway.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / immunology
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Benzazepines / pharmacology
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Biphenyl Compounds / pharmacology
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Bone Marrow Cells / cytology*
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Bone Marrow Cells / metabolism*
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Catecholamines / biosynthesis*
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Cell Division / drug effects
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Cell Division / immunology
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Cell Survival / drug effects
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Cell Survival / immunology
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Cells, Cultured
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Dopamine / biosynthesis
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Dopamine Antagonists / pharmacology
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Enzyme Inhibitors / pharmacology
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Epinephrine / biosynthesis
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Interleukin-3 / pharmacology
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Ionomycin / pharmacology
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Ionophores / pharmacology
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Mast Cells / cytology*
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Mast Cells / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Norepinephrine / biosynthesis
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Oxidation-Reduction
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Piperazines / pharmacology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Raclopride / pharmacology
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alpha-Methyltyrosine / pharmacology
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bcl-2-Associated X Protein
Substances
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Bax protein, mouse
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Benzazepines
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Biphenyl Compounds
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Catecholamines
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Dopamine Antagonists
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Enzyme Inhibitors
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Interleukin-3
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Ionophores
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Piperazines
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-2-Associated X Protein
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GR 103691
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Raclopride
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Ionomycin
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alpha-Methyltyrosine
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Dopamine
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Norepinephrine
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Epinephrine