Abstract
The transport of (3)H-histamine by the endocrine-specific (VMAT1) and neuronal (VMAT2) isoforms of the vesicular monoamine transporter has been evaluated in digitonin-permeabilized fibroblasts transfected with either VMAT1 or VMAT2. Transport of (3)H-histamine by both VMAT1 and VMAT2 was reserpine-sensitive but only transport by VMAT2 was inhibited by tetrabenazine. Maximal equilibrated levels of (3)H-histamine accumulation by VMAT2 (K(m) 300 mu M) were approximately three times greater than that mediated by VMAT1 when using a subsaturating concentration of exogenous (3)H-histamine (50 mu M). The expression of VMAT2 in histaminergic neurons in the rat brain was examined with polyclonal antipeptide antibodies specific for VMAT1 or VMAT2. VMAT2-positive and tyrosine hydroxylase-negative immunoreactive cell bodies were localized to the ventral part of the posterior hypothalamus in the region of the mamillary nuclei. The transport properties of VMAT2 and the distribution of VMAT2 in cell bodies in the tuberomammillary nucleus of the posterior hypothalamus reported here and the apparent absence of VMAT1 and VMAT2 in tissue mast cells support previous findings of reserpine-sensitive and reserpine-resistant pools of histamine in brain and peripheral tissues.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adrenergic Uptake Inhibitors / pharmacokinetics*
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Animals
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Antibody Specificity
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Biological Transport / physiology
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Cells, Cultured / chemistry
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Cells, Cultured / metabolism
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Fibroblasts / chemistry
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Histamine / pharmacokinetics*
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Hypothalamus, Posterior / chemistry
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Hypothalamus, Posterior / cytology
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Hypothalamus, Posterior / metabolism
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Immunohistochemistry
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Kinetics
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Mammillary Bodies / chemistry
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Mammillary Bodies / cytology
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Mammillary Bodies / metabolism
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Mast Cells / chemistry
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism*
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Membrane Transport Proteins*
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Neurons / chemistry
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Neurons / drug effects
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Neuropeptides*
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Neurotransmitter Agents / immunology
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Neurotransmitter Agents / metabolism*
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Rats
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Reserpine / pharmacokinetics*
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Tetrabenazine / pharmacokinetics*
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Transfection
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Tritium
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Vesicular Biogenic Amine Transport Proteins
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Vesicular Monoamine Transport Proteins
Substances
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Adrenergic Uptake Inhibitors
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Membrane Glycoproteins
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Membrane Transport Proteins
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Neuropeptides
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Neurotransmitter Agents
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Slc18a1 protein, rat
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Slc18a2 protein, rat
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Vesicular Biogenic Amine Transport Proteins
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Vesicular Monoamine Transport Proteins
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Tritium
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Histamine
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Reserpine
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Tetrabenazine